6,219 results on '"Hydroxylamines"'
Search Results
52. a-Aminooxyacetic acid derivatives acting as pro-drugs against Mycobacterium tuberculosis.
- Abstract
A preprint abstract from biorxiv.org discusses the urgent need for new anti-TB compounds due to the emergence of multidrug-resistant strains of tuberculosis. The study introduces novel antimycobacterial molecules based on a-aminooxyacetic acid core structures. These compounds, KSK-104 and KSK-106, showed potent antibacterial activity against Mycobacterium tuberculosis while being non-toxic to human cells. The study suggests that these compounds are pro-drugs that are hydrolyzed by specific enzymes, and their mechanism of action involves attacking multiple intracellular targets. However, it is important to note that this preprint has not been peer-reviewed. [Extracted from the article]
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- 2024
53. Studies from Sohag University Have Provided New Information about Selective Serotonin Reuptake Inhibitors (A Facile On-off Fluorescence Approach for Fluvoxamine Determination In Pharmaceutical Tablets; Application To Content Uniformity Testing).
- Abstract
A recent study conducted at Sohag University in Egypt has developed a new method for quantifying the antidepressant fluvoxamine. The method involves the formation of an association complex between fluvoxamine and erythrosine B in an acetate buffer solution, which results in the quenching of erythrosine B's fluorescence. The study found that this approach was effective in determining the drug in its dosage form and for content uniformity testing. The research concluded that the fluorescence of erythrosine B is quenched in a concentration-dependent manner by the ion pair complex formation with fluvoxamine. [Extracted from the article]
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- 2024
54. Patent Issued for Metalloenzyme inhibitor compounds (USPTO 11938134).
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A patent has been issued to Eikonizo Therapeutics Inc. for metalloenzyme inhibitor compounds. Metalloenzymes are enzymes that incorporate metal ions into their active sites and use them for catalytic processes. The patent discusses the importance of finding metal-binding groups that achieve a balance of potency and selectivity in order to develop safe and effective metalloenzyme inhibitors. The patent specifically focuses on the development of non-hydroxamic acid inhibitors for HDAC6, an enzyme with therapeutic potential in oncology, immunology, and neurology. The compounds described in the patent have the potential to modulate the activity of metalloenzymes and treat various diseases and disorders. [Extracted from the article]
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- 2024
55. Findings from University of British Columbia in Schizophrenia Reported (Impact of patient-specific factors on clozapine metabolism in individuals with treatment-resistant schizophrenia or schizoaffective disorder).
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- 2024
56. New Findings from Damghan University Describe Advances in Neuroscience (Effect of Fluvoxamine on Electrophysiological and Behavioral Alterations of Rats With Depression).
- Abstract
A study conducted at Damghan University in Iran explored the effects of fluvoxamine on rats with depression. The researchers divided the rats into four groups and induced chronic mild stress in three of the groups. The rats in the treatment group received daily injections of fluvoxamine. The study found that fluvoxamine effectively reduced depressive-like behaviors in the rats and also observed alterations in the electrophysiological activity of the hippocampus and the posterior cingulate cortex. The researchers concluded that fluvoxamine may reduce depression-like behaviors in animals by affecting the electrophysiological activity of these brain regions. [Extracted from the article]
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- 2024
57. Hydroxylamines as One-Atom Nitrogen Sources for Metal-Catalyzed Cycloadditions.
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Yu, Jingxun and Luan, Xinjun
- Subjects
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AZIRIDINE derivatives , *NUCLEOPHILES , *INDOLE derivatives , *TRANSITION metals , *NITROGEN - Abstract
Transition-metal-catalyzed C–N bond formation is one of the most important pathways to synthesize N-heterocycles. Hydroxylamines can be transformed into a nucleophilic reagent to react with a carbon cation or coordinate with a transition metal; it can also become an electrophilic nitrogen source to react with arenes, alkenes, and alkynes. In this short review, the progress made on transition-metal-catalyzed cycloadditions with hydroxylamines as a nitrogen source is summarized. 1 Introduction 2 Cycloaddition To Form Aziridine Derivatives 2.1 Intramolecular Cycloaddition To Form Aziridine Derivatives 2.2 Intermolecular Cycloaddition To Form Aziridine Derivatives 3 Cycloaddition To Form Indole Derivatives 4 Cycloaddition To Form Other N-Heterocycles 4.1 Aza-Heck-Type Amination Reactions 4.2 Nitrene Insertion Amination Reactions 4.3 Intramolecular Nucleophilic and Electrophilic Amination Reactions 5 Conclusion and Outlook [ABSTRACT FROM AUTHOR]
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- 2021
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58. Merging Boron with Nitrogen–Oxygen Bonds: A Review on BON Heterocycles.
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Golovanov, Ivan S. and Sukhorukov, Alexey Yu.
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Cyclic boronate esters play important roles in organic synthesis, pharmacology, supramolecular chemistry and materials science owing to their stability in air and versatile reactivity. Most of these compounds contain a B–O–C linkage with an alkoxy- or carboxylate group bound to the boron atom (e.g. boronate-diol esters, MIDA boronates). Boron chelates comprising a B–O–N motif (BON heterocycles) are much less explored, although first representatives of this class were prepared in the early 1960s. In recent years, there has been a growing interest in BON heterocycles as new chemotypes for drug design. The exocyclic B–O–N linkage, which is readily formed under mild conditions, shows surprising hydrolytic and thermal resistance. This allows the formation of BON heterocycles to be used as click-type reactions for the preparation of bioconjugates and functionally modified polymers. We believe that BON heterocycles are promising yet underrated organoboron derivatives. This review summarizes the scattered information about known types of BON heterocycles, including their synthesis, reactivity and structural data. Available applications of BON heterocycles in materials science and medicinal chemistry, along with their prospects, are also discussed. The bibliography contains 289 references. [ABSTRACT FROM AUTHOR]
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- 2021
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59. Recent advances on catalytic asymmetric hydrogenation of oximes and oxime ethers.
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Lu, Bin, Yu, Jianchao, Zhang, Xumu, and Chen, Gen-Qiang
- Subjects
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CATALYTIC hydrogenation , *ETHERS , *ASYMMETRIC synthesis , *BIOACTIVE compounds , *HYDROGENATION , *OXIMES - Abstract
[Display omitted] The asymmetric hydrogenation of imines has been well-established; however, the asymmetric hydrogenation of oximes and oxime ethers with the retention of N O bonds remains a significant challenge in the realm of asymmetric hydrogenation, due to the low reactivity and the difficulty in control of stereoselectivity. Catalytic asymmetric hydrogenation of oximes or oxime ethers represents one of the most direct and efficient method for the construction of chiral hydroxylamines, which are key structural motifs in a wide range of bioactive compounds and pharmaceuticals. This review describes the recent progress in the development of catalytic asymmetric hydrogenation of oximes and oxime ethers. We hope that this review will inspire the development of new synthetic strategies for the asymmetric synthesis of chiral hydroxylamines. [ABSTRACT FROM AUTHOR]
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- 2024
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60. N-methyl-O-benzylhydroxylamine derivatives of sialylated oligosaccharides, their synthesis and separation with reversed-phase HPLC
- Abstract
The human milk trisaccharide 3′- sialyllactose was reacted with an excess of N-methyl-O-benzylhydroxylamine (MBHA) and the product 3′- sialyllactose-MBHA was isolated in high (91%) yield by solid-phase extraction. The isomeric trisaccharide 6′-sialyllactose-MBHA was also prepared, in this case by enzymatic sialylation of lactose-MBHA. A 50/50 mixture of the two sialyllactose-MBHA derivatives was easily separated by reversed-phase HPLC. The free oligosaccharides were recovered from their respective MBHA derivatives by acid hydrolysis.
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- 2023
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61. N-methyl-O-benzylhydroxylamine derivatives of sialylated oligosaccharides, their synthesis and separation with reversed-phase HPLC
- Abstract
The human milk trisaccharide 3′- sialyllactose was reacted with an excess of N-methyl-O-benzylhydroxylamine (MBHA) and the product 3′- sialyllactose-MBHA was isolated in high (91%) yield by solid-phase extraction. The isomeric trisaccharide 6′-sialyllactose-MBHA was also prepared, in this case by enzymatic sialylation of lactose-MBHA. A 50/50 mixture of the two sialyllactose-MBHA derivatives was easily separated by reversed-phase HPLC. The free oligosaccharides were recovered from their respective MBHA derivatives by acid hydrolysis.
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- 2023
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62. Nanopore Identification of N-Acetylation by Hydroxylamine Deacetylation (NINAHD).
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Li X, Wang Y, Zhang S, Zhang P, and Huang S
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- Hydroxylamine metabolism, Acetylation, Mycobacterium smegmatis genetics, Mycobacterium smegmatis metabolism, Hydroxylamines, Nanopores
- Abstract
N -Acetyl modification, a chemical modification commonly found on biomacromolecules, plays a crucial role in the regulation of cell activities and is related to a variety of diseases. However, due to the instability of N -acetyl modification, accurate and rapid identification of N -acetyl modification with a low measurement cost is still technically challenging. Here, based on hydroxylamine deacetylation and nanopore single molecule chemistry, a universal sensing strategy for N -acetyl modification has been developed. Acetohydroxamic acid (AHA), which is produced by the hydroxylamine deacetylation reaction and serves as a reporter for N-acetylation identification, is specifically sensed by a phenylboronic acid (PBA)-modified Mycobacterium smegmatis porin A (MspA). With this strategy, N -acetyl modifications on RNA, DNA, proteins, and glycans were identified, demonstrating its generality. Specifically, histones can be treated with hydroxylamine deacetylation, from which the generated AHA can represent the amount of N -acetyl modification detected by a nanopore sensor. The unique event features of AHA also demonstrate the robustness of sensing against other interfering analytes in the environment.
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- 2024
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63. A novel mechanism for dissimilatory nitrate reduction to ammonium in Acididesulfobacillus acetoxydans .
- Author
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Egas RA, Kurth JM, Boeren S, Sousa DZ, Welte CU, and Sánchez-Andrea I
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- Nitrites metabolism, Ecosystem, Denitrification, Bacteria metabolism, Hydroxylamine, Nitrite Reductases metabolism, Nitrogen, Hydroxylamines, Sulfates, Nitrates metabolism, Ammonium Compounds metabolism
- Abstract
The biological route of nitrate reduction has important implications for the bioavailability of nitrogen within ecosystems. Nitrate reduction via nitrite, either to ammonium (ammonification) or to nitrous oxide or dinitrogen (denitrification), determines whether nitrogen is retained within the system or lost as a gas. The acidophilic sulfate-reducing bacterium (aSRB) Acididesulfobacillus acetoxydans can perform dissimilatory nitrate reduction to ammonium (DNRA). While encoding a Nar-type nitrate reductase, A. acetoxydans lacks recognized nitrite reductase genes. In this study, A. acetoxydans was cultivated under conditions conducive to DNRA. During cultivations, we monitored the production of potential nitrogen intermediates (nitrate, nitrite, nitric oxide, hydroxylamine, and ammonium). Resting cell experiments were performed with nitrate, nitrite, and hydroxylamine to confirm their reduction to ammonium, and formed intermediates were tracked. To identify the enzymes involved in DNRA, comparative transcriptomics and proteomics were performed with A. acetoxydans growing under nitrate- and sulfate-reducing conditions. Nitrite is likely reduced to ammonia by the previously undescribed nitrite reductase activity of the NADH-linked sulfite reductase AsrABC, or by a putatively ferredoxin-dependent homolog of the nitrite reductase NirA (DEACI_1836), or both. We identified enzymes and intermediates not previously associated with DNRA and nitrosative stress in aSRB. This increases our knowledge about the metabolism of this type of bacteria and helps the interpretation of (meta)genome data from various ecosystems on their DNRA potential and the nitrogen cycle.IMPORTANCENitrogen is crucial to any ecosystem, and its bioavailability depends on microbial nitrogen-transforming reactions. Over the recent years, various new nitrogen-transforming reactions and pathways have been identified, expanding our view on the nitrogen cycle and metabolic versatility. In this study, we elucidate a novel mechanism employed by Acididesulfobacillus acetoxydans , an acidophilic sulfate-reducing bacterium, to reduce nitrate to ammonium. This finding underscores the diverse physiological nature of dissimilatory reduction to ammonium (DNRA). A. acetoxydans was isolated from acid mine drainage, an extremely acidic environment where nitrogen metabolism is poorly studied. Our findings will contribute to understanding DNRA potential and variations in extremely acidic environments., Competing Interests: The authors declare no conflict of interest.
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- 2024
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64. Respiratory virus coinfections during the COVID-19 pandemic: epidemiologic analysis and clinical outcomes from the Phase 2/3 molnupiravir trial (MOVe-OUT).
- Author
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Johnson MG, Strizki JM, Jensen E, Cohen J, Katlama C, Fishchuk R, Ponce-de-León A, Fourie N, Cheng C-Y, McCoy D, Vesnesky M, Norice CT, Zhang Y, Williams-Diaz A, Brown ML, Carmelitano P, Grobler JA, Paschke A, and De Anda C
- Subjects
- Adult, Humans, SARS-CoV-2, Pandemics, RNA, COVID-19 epidemiology, Coinfection drug therapy, Coinfection epidemiology, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
This exploratory post hoc analysis assessed the incidence of respiratory viral coinfections and their impact on clinical outcomes in non-hospitalized adults with mild-to-moderate coronavirus disease-2019 (COVID-19) treated with molnupiravir versus placebo for 5 days in the Phase 2/3 MOVe-OUT trial (NCT04575597), which took place in October 2020 to January 2021 (Phase 2, n = 302) and May 2021 to October 2021 (Phase 3, n = 1,433). Among 1,735 total randomized participants, 1,674 had a baseline respiratory pathogen panel (NxTAG Respiratory Pathogen Panel for the Luminex MAGPIX instrument) performed and 69 (4.1%) were coinfected with at least one additional respiratory viral pathogen. Human rhinovirus/enterovirus (39/69, 56.5%) was the most common coinfection detected at baseline. In the modified intention-to-treat population, two participants with coinfecting respiratory RNA viruses were hospitalized and received respiratory interventions through Day 29, and none died; one participant in the molnupiravir group was coinfected with human rhinovirus/enterovirus, and one participant in the placebo group was coinfected with human metapneumovirus. Hospitalization or death occurred in 6.2% and 9.0% of non-coinfected participants in the molnupiravir versus placebo group, respectively, and over 90% did not require respiratory interventions. Most coinfecting respiratory RNA viruses detected at baseline were not detected at the end of therapy in both the molnupiravir and placebo groups. In summary, participants coinfected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to be hospitalized or die, or require respiratory interventions, compared to participants who were not coinfected with another respiratory RNA virus at baseline in both groups., Importance: Respiratory viral coinfections are known to occur with coronavirus disease-2019 (COVID-19). In a cohort of non-hospitalized adults with mild-to-moderate COVID-19 treated with molnupiravir versus placebo in the MOVe-OUT trial during October 2020 to October 2021, 4.1% of participants had a documented viral coinfection; human rhinovirus/enterovirus was the most common pathogen detected with the NxTAG Respiratory Pathogen Panel assay. Participants who had a coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and another respiratory RNA virus were not more likely to have worse clinical outcomes compared to those participants without a viral coinfection, and many coinfecting respiratory RNA viruses were no longer detected at the end of the 5-day treatment period in both groups., Competing Interests: Matthew G. Johnson, Julie M. Strizki, Erin Jensen, Dorothy McCoy, Mary Vesnesky, Carmelle T. Norice, Ying Zhang, Angela Williams-Diaz, Michelle L. Brown, Patricia Carmelitano, Jay A. Grobler, Amanda Paschke, and Carisa De Anda are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. Jonathan Cohen: no conflicts of interest. Christine Katlama: no conflicts of interest. Roman Fishchuk: no conflicts of interest. Alfredo Ponce-de-León: Grants: NIH ATCC 1-4; Advisory boards: LATAM MSD, Gilead; Speaker: MSD, Gilead, Becton Dickinson, Qiagen. Nyda Fourie: no conflicts of interest. Chien-Yu Cheng: no conflicts of interest.
- Published
- 2024
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65. Small-molecule antiviral treatments for COVID-19: A systematic review and network meta-analysis.
- Author
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Zheng B, Zhao Q, Yang W, Feng P, Xin C, Ying Y, Yang B, Han B, Zhu J, Zhang M, and Li G
- Subjects
- Humans, Network Meta-Analysis, Retrospective Studies, Ritonavir therapeutic use, Antiviral Agents adverse effects, COVID-19, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
Objective: This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19)., Methods: Seven databases were searched from their inception to 01 June 2023. The risk of bias in randomised controlled trials and retrospective studies was evaluated individually using the Cochrane risk-of-bias tool and Newcastle Ottawa Scale., Results: In total, 160 studies involving 933 409 COVID-19 patients were evaluated. Compared with placebo or standard of care, proxalutamide demonstrated remarkable efficacy in reducing mortality rates, hospitalisation rates, serious adverse events, and the need for mechanical ventilation. Furthermore, it significantly enhanced both the rate of clinical improvement and expedited the duration of clinical recovery when compared with control groups. In patients with mild-to-moderate COVID-19, proxalutamide exhibited the above advantages, except for mortality reduction. Triazavirin was the most effective treatment for reducing the time required for viral clearance and improving the discharge rate. Leritrelvir and VV116 were ranked first in terms of enhancing the viral clearance rate on days 7 and 14, respectively. Molnupiravir was the most effective treatment for reducing the need for oxygen support. Overall, these findings remained consistent across the various subgroups., Conclusions: A thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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66. Association between high-dose molnupiravir and COVID-19 mortality rate.
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Chang LC, Chen IW, and Hung KC
- Subjects
- Humans, COVID-19 mortality, Cytidine analogs & derivatives, Hydroxylamines
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- 2024
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67. In reply to comment on: Association between high-dose molnupiravir and COVID-19 mortality rate.
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Chen Z and Tian F
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- Humans, COVID-19 mortality, Cytidine analogs & derivatives, Hydroxylamines
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- 2024
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68. Molnupiravir inhibits human norovirus and rotavirus replication in 3D human intestinal enteroids.
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Santos-Ferreira N, Van Dycke J, Chiu W, Neyts J, Matthijnssens J, and Rocha-Pereira J
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- Humans, Diarrhea drug therapy, Antiviral Agents pharmacology, Rotavirus, Norovirus, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
Human norovirus (HuNoV) and human rotavirus (HRV) are the leading causes of gastrointestinal diarrhea. There are no approved antivirals and rotavirus vaccines are insufficient to cease HRV associated mortality. Furthermore, treatment of chronically infected immunocompromised patients is limited to off-label compassionate use of repurposed antivirals with limited efficacy, highlighting the urgent need of potent and specific antivirals for HuNoV and HRV. Recently, a major breakthrough in the in vitro cultivation of HuNoV and HRV derived from the use of human intestinal enteroids (HIEs). The replication of multiple circulating HuNoV and HRV genotypes can finally be studied and both in the same non-transformed and physiologically relevant model. Activity of previously described anti-norovirus or anti-rotavirus drugs, such as 2'-C-methylcytidine (2CMC), 7-deaza-2'-C-methyladenosine (7DMA), nitazoxanide, favipiravir and dasabuvir, was assessed against clinically relevant human genotypes using 3D-HIEs. 2CMC showed the best activity against HuNoV GII.4, while 7DMA was the most potent antiviral against HRV. We identified the anti-norovirus and -rotavirus activity of molnupiravir and its active metabolite, N4-hydroxycytidine (NHC), a broad-spectrum antiviral used to treat coronavirus disease 2019 (COVID-19). Molnupiravir and NHC inhibit HuNoV GII.4, HRV G1P[8], G2P[4] and G4P[6] in 3D-HIEs with high selectivity and show a potency comparable to 2CMC against HuNoV. Moreover, molnupiravir and NHC block HRV viroplasm formation, but do not alter its size or subcellular localization. Taken together, molnupiravir inhibits both HuNoV and HRV replication, suggesting that the drug could be a candidate for the treatment of patients chronically infected with either one of these diarrhea causing viruses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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69. Evaluation of physicians prescribing of COVID-19 guideline-directed outpatient treatments in a primary care walk-in clinic.
- Author
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Denning K, Sheppard J, and Carico R Jr
- Subjects
- Humans, Ritonavir therapeutic use, Outpatients, COVID-19 Drug Treatment, Retrospective Studies, Primary Health Care, Antiviral Agents therapeutic use, COVID-19, Physicians, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Background: Coronavirus disease 2019 (COVID-19) is a respiratory virus that has afflicted millions of individuals in the United States. A few medications have been determined to be beneficial for outpatient treatment. The medications in use against mild-to-moderate COVID-19 in the outpatient setting during the study period are nirmatrelvir-ritonavir, remdesivir, molnupiravir, and bebtelovimab. Proper assessment and treatment of patients with mild-to-moderate COVID-19 in the outpatient setting is critical to reducing rates of disease progression and hospitalization., Objective: This study aimed to evaluate the appropriateness of the prescribing by internal medicine physicians for mild-to-moderate Coronavirus disease 2019 (COVID-19) infections based on the National Institutes of Health (NIH) guideline-directed COVID-19 outpatient treatment options., Methods: This is a retrospective chart review examining the outpatient treatment of mild-to-moderate COVID-19 by internal medicine physicians between February 2022 and August 2022. Patients were eligible if they were 18 years or older, had a positive home or polymerase chain reaction (PCR) test, completed a telehealth visit within 7 days of the positive test, and were prescribed either nirmatrelvir-ritonavir, remdesivir, molnupiravir, or bebtelovimab for COVID-19 treatment. The primary end point was the appropriateness of COVID-19 treatment in the outpatient setting based on NIH guidelines, patient characteristics, and prescribing information for the medications. The secondary end point was hospitalization within 30 days of initiation of outpatient COVID-19 treatment. The presence or absence of a clinical pharmacist consultation at the time of prescribing was recorded as a process measure., Results: A total of 376 encounters were assessed, of which 226 were included and analyzed. A total of 210 participants (93%) received nirmatrelvir-ritonavir. The remaining participants received molnupiravir or bebtelovimab. Overall, guideline-concordant treatment for mild-to-moderate COVID-19 was prescribed for 200 participants (88%). Among patient characteristics, only glomerular filtration rate (GFR) had a statistically significant difference between groups prescribed medication for the treatment of mild-to-moderate COVID-19. Fifty-six participants (25%) received clinical pharmacist consultation. Three participants were hospitalized for COVID-19 within 30 days of receiving an appropriately prescribed medication for treatment. Nirmatrelvir-ritonavir was the only medication potentially prescribed inappropriately due to lack of being renally dose adjusted and the extensive drug-drug interactions., Conclusion: Nirmatrelvir-ritonavir was the most prescribed medication for the treatment of mild-to-moderate COVID-19, consistent with its position as first-line therapy and widespread accessibility. The study results will inform future educational opportunities, such as in-service presentations and handouts, that may improve the prescribing of outpatient treatment for mild-to-moderate COVID-19 moving forward., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
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- 2024
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70. Successive Protein Extraction Using Hydroxylamine to Increase the Depth of Proteome Coverage in Fresh, Forensic, and Archaeological Bones.
- Author
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Gilbert C, Bathany K, Claverol S, Scanvion Q, Hedouin V, Bertrand B, and Tokarski C
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- Hydroxylamine, Bone and Bones, Hydroxylamines, Proteome, Proteomics methods
- Abstract
Proteomics is continually being applied to a wider range of applications, now including the analysis of archaeological samples and anatomical specimens, particularly collagen-containing tissues such as bones and teeth. Here, we present the application of a chemical digestion-based proteomics sample preparation protocol to the analysis of fresh, anatomical, and archaeological samples. We describe and discuss two protocols: one that uses hydroxylamine as an additional step of the proteomic workflow, applied to the insoluble fraction, and another that applies hydroxylamine directly on demineralized bones and teeth. We demonstrate the additional information that can be extracted using both protocols, including an increase in the sequence coverage and number of peptides detected in modern and archaeological samples and an increase in the number of proteins identified in archaeological samples. By targeting research related to collagens or extracellular matrix proteins, the use of this protocol will open new insights, considering both fresh and ancient mineralized samples.
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- 2024
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71. Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.
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Standing JF, Buggiotti L, Guerra-Assuncao JA, Woodall M, Ellis S, Agyeman AA, Miller C, Okechukwu M, Kirkpatrick E, Jacobs AI, Williams CA, Roy S, Martin-Bernal LM, Williams R, Smith CM, Sanderson T, Ashford FB, Emmanuel B, Afzal ZM, Shields A, Richter AG, Dorward J, Gbinigie O, Van Hecke O, Lown M, Francis N, Jani B, Richards DB, Rahman NM, Yu LM, Thomas NPB, Hart ND, Evans P, Andersson M, Hayward G, Hood K, Nguyen-Van-Tam JS, Little P, Hobbs FDR, Khoo S, Butler C, Lowe DM, and Breuer J
- Subjects
- Adult, Humans, Outpatients, Antibody Formation, Antibodies, Viral, Antiviral Agents therapeutic use, SARS-CoV-2 genetics, COVID-19, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031., (© 2024. The Author(s).)
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- 2024
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72. Could Molnupiravir Be the First-Line Alternative Oral Antiviral Agent for COVID-19 Patients at High Risk?
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Lee JY
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- Humans, Hydroxylamines, Antiviral Agents therapeutic use, COVID-19, Cytidine analogs & derivatives
- Abstract
Competing Interests: The author has no potential conflicts of interest to disclose.
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- 2024
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73. Determining and Comparing the Real-World Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Patients Hospitalized With COVID-19.
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Jang YR, Oh Y, and Kim JY
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- Adult, Humans, COVID-19 Drug Treatment, Retrospective Studies, Ritonavir therapeutic use, Disease Progression, Antiviral Agents therapeutic use, COVID-19, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Background: Current guidelines recommend using nirmatrelvir-ritonavir for coronavirus disease 2019 (COVID-19) treatment, but its potential drug interactions and contraindications limit its applicability in certain categories of patients. The aim of the study was to evaluate the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in managing COVID-19 among hospitalized patients., Methods: We conducted a retrospective cohort study among hospitalized COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir and did not require baseline supplemental oxygen from February 2022 to January 2023. We compared the effectiveness of molnupiravir and nirmatrelvir-ritonavir with a focus on disease progression., Results: The study included 401 high-risk, hospitalized adult COVID-19 patients who received molnupiravir or nirmatrelvir-ritonavir. No significant difference was found in disease progression, the composite outcome of disease progression (4.0% vs. 1.4%, P = 0.782), and O
2 supplementation via nasal prong (21.8% vs. 14.8%, P = 0.115) between the patients treated with molnupiravir and those treated with nirmatrelvir-ritonavir. This finding was similar after 1:1 propensity-score matching. In the multivariate analysis, molnupiravir treatment was not significantly associated with progression to severe disease., Conclusion: In conclusion, our findings suggest that similar to nirmatrelvir-ritonavir, molnupiravir has a distinct potential role in COVID-19 treatment, transcending its current perceived status as only a secondary option., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)- Published
- 2024
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74. Characteristics and Outcomes of US Veterans With Immunocompromised Conditions at High Risk of SARS-CoV-2 Infection With or Without Receipt of Oral Antiviral Agents.
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Gentry CA, Nguyen PN, Thind SK, Kurdgelashvili G, and Williams RJ 2nd
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- Humans, SARS-CoV-2, Ritonavir therapeutic use, Antiviral Agents therapeutic use, COVID-19 epidemiology, Veterans, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Objectives: Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US veterans with immunocompromised conditions prescribed oral antivirals with those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection., Methods: This was a retrospective, observational, nationwide propensity-matched analysis of US veterans with immunocompromised conditions who developed documented SARS-CoV-2 infection. The primary outcome was the composite of any hospitalization or death within 30 days of diagnosis. Secondary outcomes included 30-day comparative rates of (1) any hospitalization, (2) death, (3) intensive care requirement, and (4) subset analyses of outcomes by oral antiviral used and vaccination status., Results: The composite primary outcome was significantly lower in patients receiving oral antiviral therapy compared with those who did not (23/390 [5.9%] vs 57/390 [14.6%]; odds ratio, 0.37; 95% confidence interval, .22-.61). This difference was driven largely by fewer deaths in the oral antiviral group (1/390 [0.3%] vs 19/390 [4.9%]; odds ratio, 0.05; 95% confidence interval, .007-.38). There was no significant difference in rate of intensive care requirement. The composite outcome was improved in vaccinated patients (completing the first series or first booster dose) who received oral antiviral agents compared with those who did not receive oral antiviral agents. Compared with those prescribed nirmatrelvir-ritonavir, patients given molnupiravir were older, had a higher incidence of cautions/contraindications, greater prevalence of tobacco use, and more cardiovascular complications., Conclusions: Use of molnupiravir or nirmatrelvir-ritonavir was associated with lower incidences of hospitalization or death within 30 days of diagnosis in US veterans with immunocompromised conditions, regardless of vaccination status. These findings support the use of either oral antiviral in this patient population., Competing Interests: Potential conflicts of interest. G. K. reports grants or contracts for serving as local principal investigator for 2 Cooperative Studies Program studies (funded by Veterans Health Administration) at Oklahoma City Veterans Affairs Healthcare System; a role as Board member of Northcare—nonprofit Mental health provider organization, Oklahoma City, OK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)
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- 2024
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75. Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study.
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Chen MP, Jiang DX, Rang JX, Zhuo HB, and Zhou ZG
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- Adult, Humans, Retrospective Studies, COVID-19 Drug Treatment, Antiviral Agents therapeutic use, Ritonavir therapeutic use, COVID-19, Hydroxylamines, Deoxycytidine analogs & derivatives, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Azides, Leucine
- Abstract
This study aimed to explore the effectiveness and safety of azvudine, nirmatrelvir/ritonavir, and molnupiravir in adult patients with mild-to-moderate COVID-19. This retrospective cohort study included patients with mild-to-moderate COVID-19 (asymptomatic, mild, and common types) at the First Hospital of Changsha (Hunan Province, China) between March and November 2022. Eligible patients were classified into the azvudine, nirmatrelvir/ritonavir, or molnupiravir groups according to the antiviral agents they received. The outcomes were the times to nucleic acid negative conversion (NANC). This study included 157 patients treated with azvudine (n = 66), molnupiravir (n = 66), or nirmatrelvir/ritonavir (n = 25). There were no statistically significant differences in the time from diagnosis to NANC among the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups [median, 9 (95% CI 9-11) vs. 11 (95% CI 10-12) vs. 9 (95% CI 8-12) days, P = 0.15], time from administration to NANC [median, 9 (95% CI 8-10) vs. 10 (95% CI 9.48-11) vs. 8.708 (95% CI 7.51-11) days, P = 0.50], or hospital stay [median, 11 (95% CI 11-13) vs. 13 (95% CI 12-14) vs. 12 (95% CI 10-14) days, P = 0.14], even after adjustment for sex, age, COVID-19 type, comorbidities, Ct level, time from diagnosis to antiviral treatment, and number of symptoms. The cumulative NANC rates in the azvudine, molnupiravir, and nirmatrelvir/ritonavir groups were 15.2%/12.3%/16.0% at day 5 (P = 0.858), 34.8%/21.5%/32.0% at day 7 (P = 0.226), 66.7%/52.3%/60.0% at 10 days (P = 0.246), and 86.4%/86.2%/80.0% at day 14 (P = 0.721). No serious adverse events were reported. Azvudine may be comparable to nirmatrelvir/ritonavir and molnupiravir in adult patients with mild-to-moderate COVID-19 regarding time to NANC, hospital stay, and AEs., (© 2024. The Author(s).)
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- 2024
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76. Site-Specific Identification of Protein S-Acylation by IodoTMT0 Labeling and Immobilized Anti-TMT Antibody Resin Enrichment.
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Cai J, Song M, Li M, Merchant M, Benz F, McClain C, and Klein J
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- Animals, Mice, Humans, Acylation, Lipoylation, Hydroxylamine, Hydroxylamines, Proteins, Protein Processing, Post-Translational
- Abstract
Protein S-acylation is a reversible post-translational modification (PTM). It is present on diverse proteins and has important roles in regulating protein function. Aminolysis with hydroxylamine is widely used in the global identification of the PTM. However, the identification is indirect. Distinct criteria have been used for identification, and the false discovery rate has not been addressed. Here, we report a site-specific method for S-acylation identification based on tagging of S-acylation sites with iodoTMT0. Efforts to improve the performance of the method and confidence of identification are discussed, highlighting the importance of reducing contaminant peptides and keeping the recovery rate consistent between aliquots with or without hydroxylamine treatment. With very stringent criteria, presumptive S-acylation sites of 269, 684, 695, and 780 were identified from HK2 cells, HK11 cells, mouse brain, and mouse liver samples, respectively. Among them, the newly identified protein S-acylation sites are equivalent to 34% of human and 24% of mouse S-acylation sites reported previously. In addition, false-positive rates for S-acylation identification and S-acylation abundances were estimated. Significant differences in S-acylation abundance were found from different samples (from 0.08% in HK2 cells to 0.76% in mouse brain), and the false-positive rates were significantly higher for samples with a low abundance of S-acylation.
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- 2024
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77. Molnupiravir: Mechanism of action, clinical, and translational science.
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Maas BM, Strizki J, Miller RR, Kumar S, Brown M, Johnson MG, Cheng M, De Anda C, Rizk ML, and Stone JA
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- Humans, Cytidine pharmacology, Hydroxylamines, SARS-CoV-2, Translational Science, Biomedical, Cytidine analogs & derivatives, Ribonucleosides
- Abstract
Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog N-hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC-triphosphate (NHC-TP). NHC-TP serves as a competitive substrate for viral RNA-dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent. Molnupiravir has demonstrated activity against SARS-CoV-2 both clinically and preclinically and has a high barrier to development of viral resistance. Little to no molnupiravir is observed in plasma due to rapid hydrolysis to NHC. Maximum concentrations of NHC are reached at 1.5 h following administration in a fasted state. The effective half-life of NHC is 3.3 h, reflecting minimal accumulation in the plasma following twice-daily (Q12H) dosing. The terminal half-life of NHC is 20.6 h. NHC-TP exhibits a flatter profile with a lower peak-to-trough ratio compared with NHC, which supports Q12H dosing. Renal and hepatic pathways are not major routes of elimination, as NHC is primarily cleared by metabolism to uridine and cytidine, which then mix with the endogenous nucleotide pools. In a phase III study of nonhospitalized patients with COVID-19 (MOVe-OUT), 5 days of treatment with 800 mg molnupiravir Q12H significantly reduced the incidence of hospitalization or death compared with placebo. Patients treated with molnupiravir also had a greater reduction in SARS-CoV-2 viral load and improved clinical outcomes, compared with those receiving placebo. The clinical effectiveness of molnupiravir has been further demonstrated in several real-world evidence studies. Molnupiravir is currently authorized or approved in more than 25 countries., (© 2024 Merck Sharp and Dohme LLC. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
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- 2024
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78. Response of marine anammox bacteria to long-term hydroxylamine stress: Nitrogen removal performance and microbial community dynamics.
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Zhao N, Qiu Y, Qu Z, and Li J
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- Hydroxylamine, Wastewater, Nitrogen analysis, Denitrification, Anaerobic Ammonia Oxidation, Bacteria, Hydroxylamines, Ammonium Compounds, Microbiota
- Abstract
The response of anammox bacteria to hydroxylamine has not been well explained. Herein, hydroxylamine was long-term added as the sole substrate to marine anammox bacteria (MAB) in saline wastewater treatment for the first time. MAB could tolerate 5 mg/L hydroxylamine. However, MAB activity was inhibited by the high dose of hydroxylamine (40 mg/L), and hydroxylamine removal efficiency was only 3 %. Remarkably, when hydroxylamine reached 20 mg/L, ammonium was produced the most at 2.88 mg/L, mainly by the hydroxylamine and hydrazine disproportionations. Besides, the relative abundance of Candidatus Scalindua decreased from 4.6 % to 0.6 % as the hydroxylamine increased from 0 to 40 mg/L. MAB secreted more extracellular polymeric substances to resist hydroxylamine stress. However, long-term hydroxylamine loading led to the disintegration of MAB granules. This work shed light on the response of MAB to hydroxylamine in saline wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2024
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79. Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy.
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El-Shafai NM, Mostafa YS, Ramadan MS, and M El-Mehasseb I
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- Humans, Cellulose pharmacology, Antiviral Agents pharmacology, Anti-Bacterial Agents pharmacology, Zinc Oxide pharmacology, Zinc Oxide chemistry, COVID-19, Nanoparticles chemistry, Cytidine analogs & derivatives, Flavonoids, Hydroxylamines, Plant Extracts
- Abstract
The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-Vis spectroscopy under room temperature and different pH. The release efficiency of the MOL drug is calculated to be 65% (pH 6.8) and 69% (pH 7.4). The modified MOL drug displays 71% (pH 6.8) and 78% (pH 7.4) for CNC@Pyc.MOL nanocomposite, while CNC@Pyc.MOL.ZnO nanocomposite gave values at 76% (pH 6.8) and 78% (pH 7.4), the efficiency recorded after 19 h. The biological activity of the MOL-drug and modified MOL-drug is measured, and the cytotoxicity is performed by SRB technique, where the self-assembly (CNC@Pyc) appears to be a safe healthy, and high viability against the examined cell line. The antioxidant activity and anti-inflammatory are evaluated, where the nanocomposite that has ZnO NPs (CNC@Pyc.MOL.ZnO) gave high efficiency compared to the composite without ZnO NPs. The CPE-inhibition assay is used to identify potential antivirals against CVID-19 (229E virus), the viral inhibition (%) was reported at 37.6 % (for 800 µg/ml) and 18.02 % (for 400 µg/ml) of CNC@Pyc.MOL.ZnO. So, the modified MOL-drug was suggested as a replacement drug for the therapy of COVID-19 compared to MOL-drug, but the results need clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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80. Additional analyses support superior efficacy of nirmatrelvir/ritonavir over molnupiravir for COVID-19.
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Chang LC, Chen IW, and Hung KC
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- Humans, COVID-19 Drug Treatment, Antiviral Agents therapeutic use, Ritonavir therapeutic use, COVID-19, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
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- 2024
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81. Amino acid and protein specificity of protein fatty acylation in C. elegans .
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Zhang B, Yu Y, Fox BW, Liu Y, Thirumalaikumar VP, Skirycz A, Lin H, and Schroeder FC
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- Animals, Acylation, Fatty Acids, Hydroxylamine, Hydroxylamines, Amino Acids, Caenorhabditis elegans
- Abstract
Protein lipidation plays critical roles in regulating protein function and localization. However, the chemical diversity and specificity of fatty acyl group utilization have not been investigated using untargeted approaches, and it is unclear to what extent structures and biosynthetic origins of S -acyl moieties differ from N - and O -fatty acylation. Here, we show that fatty acylation patterns in Caenorhabditis elegans differ markedly between different amino acid residues. Hydroxylamine capture revealed predominant cysteine S -acylation with 15-methylhexadecanoic acid (isoC17:0), a monomethyl branched-chain fatty acid (mmBCFA) derived from endogenous leucine catabolism. In contrast, enzymatic protein hydrolysis showed that N-terminal glycine was acylated almost exclusively with straight-chain myristic acid, whereas lysine was acylated preferentially with two different mmBCFAs and serine was acylated promiscuously with a broad range of fatty acids, including eicosapentaenoic acid. Global profiling of fatty acylated proteins using a set of click chemistry-capable alkyne probes for branched- and straight-chain fatty acids uncovered 1,013 S -acylated proteins and 510 hydroxylamine-resistant N - or O -acylated proteins. Subsets of S -acylated proteins were labeled almost exclusively by either a branched-chain or a straight-chain probe, demonstrating acylation specificity at the protein level. Acylation specificity was confirmed for selected examples, including the S -acyltransferase DHHC-10. Last, homology searches for the identified acylated proteins revealed a high degree of conservation of acylation site patterns across metazoa. Our results show that protein fatty acylation patterns integrate distinct branches of lipid metabolism in a residue- and protein-specific manner, providing a basis for mechanistic studies at both the amino acid and protein levels., Competing Interests: Competing interests statement:H.L. is a founder of, consultant, and a stockholder for Sedec Therapeutics. F.C.S. is a founder of, consultant, and a stockholder for Ascribe Bioscience and Holoclara Inc.
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- 2024
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82. Novel Epigenetic Modifiers of Histones Presenting Potent Inhibitory Effects on Adenoid Cystic Carcinoma Stemness and Invasive Properties.
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Pina PSS, Jang Y, Emerick C, Scarini JF, Sousa SCOM, Squarize CH, and Castilho RM
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- Humans, Histones metabolism, Cell Line, Tumor, Epigenesis, Genetic, Neoplasm Invasiveness, Carcinoma, Adenoid Cystic drug therapy, Carcinoma, Adenoid Cystic genetics, Carcinoma, Adenoid Cystic metabolism, Salivary Gland Neoplasms pathology, Hydroxylamines, Quinolines
- Abstract
Adenoid cystic carcinoma (ACC) is a rare neoplasm known for its indolent clinical course, risk of perineural invasion, and late onset of distant metastasis. Due to the scarcity of samples and the tumor's rarity, progress in developing effective treatments has been historically limited. To tackle this issue, a high-throughput screening of epigenetic drugs was conducted to identify compounds capable of disrupting the invasive properties of the tumor and its cancer stem cells (CSCs). ACC cells were screened for changes in tumor viability, chromatin decondensation, Snail inhibition along tumor migration, and disruption of cancer stem cells. Seven compounds showed potential clinical interest, and further validation showed that Scriptaid emerged as a promising candidate for treating ACC invasion. Scriptaid demonstrated a favorable cellular toxicity index, effectively inhibited Snail expression, induced hyperacetylation of histone, reduced cell migration, and effectively disrupted tumorspheres. Additionally, LMK235 displayed encouraging results in four out of five validation assays, further highlighting its potential in combating tumor invasion in ACC. By targeting the invasive properties of the tumor and CSCs, Scriptaid and LMK235 hold promise as potential treatments for ACC, with the potential to improve patient outcomes and pave the way for further research in this critical area.
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- 2024
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83. Two short approaches to the COVID-19 drug β-D- N 4 -hydroxycytidine and its prodrug molnupiravir.
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Persaud KE, Sahu RR, Neary MC, Kapdi AR, and Lakshman MK
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- Humans, Hydroxylamines, Antiviral Agents, COVID-19, Prodrugs, Cytidine analogs & derivatives
- Abstract
Molnupiravir, the prodrug for β-D- N
4 -hydroxycytidine (NHC), is marketed by Merck as Lagevrio™ against mild-moderate COVID-19, under FDA emergency use authorization. It is the first oral drug against the disease. This work describes two synthetic approaches to NHC and molnupiravir by amide activation in uridine with a peptide-coupling agent and with a 4-chloropyrimidinone nucleoside intermediate.- Published
- 2024
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84. Real-World Effectiveness Study of Nirmatrelvir-Ritonavir or Molnupiravir in Hospitalized Unvaccinated Patients with Chronic Respiratory Diseases and Moderate COVID-19 at Presentation.
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Kwok WC, Tam TCC, Ho JCM, Lam DCL, Ip MS, and Ho PL
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- Adult, Humans, Retrospective Studies, Ritonavir adverse effects, COVID-19 Drug Treatment, Outpatients, Antiviral Agents adverse effects, Pulmonary Disease, Chronic Obstructive, COVID-19, Respiration Disorders, Respiratory Insufficiency diagnosis, Respiratory Insufficiency drug therapy, Respiratory Insufficiency etiology, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases., Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023., Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups., Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission., Competing Interests: All authors report no conflicts of interest in this work., (© 2024 Kwok et al.)
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- 2024
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85. Use of molnupiravir: A Danish nationwide drug utilization study.
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Ladebo L, Rasmussen L, Jensen PB, Lindahl M, Øvrehus A, Hallas J, and Reilev M
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- Adult, Male, Humans, Female, Aged, Cognition, Drug Utilization, SARS-CoV-2, Denmark epidemiology, Antiviral Agents, COVID-19 epidemiology, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
Purpose: To describe utilization patterns, characteristics of users and prescribers of the new oral antiviral medication, molnupiravir, indicated for mild-to-moderate COVID-19., Methods: Using nationwide registries, we identified all Danish adults who filled a prescription for molnupiravir from December 16th, 2021, to August 31st, 2022. We described weekly incidence rates and patient characteristics over time, prescriber characteristics as well as time between molnupiravir initiation and a positive SARs-CoV-2 test. Patient characteristics were compared to matched, untreated SARS-CoV-2 positive reference groups., Results: By August 31st, 2022, 5847 individuals had filled a prescription for molnupiravir. The incidence rate gradually increased to 16 weekly prescriptions per 1000 RT-PCR SARS-CoV-2 positives. Users of molnupiravir were most often men (55% vs. 45% women). The majority (81%) had a positive RT-PCR SARS-CoV-2 test and few (2.9%) redeemed molnupiravir outside the recommended window of 5 days from the positive test result. Compared to matched, untreated SARS-CoV-2 positive reference groups, users of molnupiravir had a median age of 74 years versus 49 years, a higher proportion resided in a nursing home (12% vs. 1.5%) and had a higher number of comorbidities (median of 3 vs. 0); most commonly hypertension (38%), chronic lung disease (35%), diabetes (20%) and mood disorders (20%). General practitioners were the primary prescribers of molnupiravir (91%)., Conclusions: Molnupiravir was mainly prescribed by general practitioners to RT-PCR SARS-CoV-2 positive individuals who had a potentially increased risk of severe COVID-19. Though some off-label prescribing occurred, our study indicates a high level of adherence to contemporary guidelines., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)
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- 2024
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86. Effect of pre-hospitalization use of oral antiviral agents on reducing critical illness and mortality for patients with COVID-19 pneumonia.
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Yii YC, Shih HM, Chen CL, Lai ZL, Hsu YL, Lai CH, Hsueh PR, and Cho DY
- Subjects
- Humans, COVID-19 Vaccines, Ritonavir therapeutic use, Critical Illness, Retrospective Studies, Hospitalization, Antiviral Agents therapeutic use, COVID-19, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Objectives: This study aimed to evaluate the effect of administering nirmatrelvir/ritonavir and molnupiravir before hospitalisation on subsequent critical illness among patients with COVID-19 pneumonia., Methods: This retrospective cohort study included patients with COVID-19 pneumonia who required hospitalisation between 1 January 1 2022 and 31 August 2022. The primary outcomes were the development of critical illness, including intensive care unit admission, use of mechanical ventilation, or mortality. A multivariate logistic regression analysis was conducted to assess the varying risks of critical illness and mortality. A total of 1,011 COVID-19 patients were analysed. Among them, 304 (30.1%) received molnupiravir and 131 (13.0%) received nirmatrelvir/ritonavir before hospitalisation., Results: There were significant reductions for critical illness (adjusted odds ratio 0.29, 95% confidence interval 0.21-0.39, P < 0.001) and mortality (adjusted odds ratio 0.40, 95% confidence interval 0.27-0.59, P < 0.001) in patients receiving oral antivirals compared with those who did not. No significant differences in critical illness were observed between molnupiravir and nirmatrelvir/ritonavir. The combination of COVID-19 vaccines and oral antivirals can further reduce the risk of critical illness in high-risk populations., Conclusion: Administering molnupiravir and nirmatrelvir/ritonavir before hospitalisation reduced the risk of COVID-19 patients with moderate to severe pneumonia progressing to critical illness and mortality., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)
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- 2024
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87. Efficacy and safety of antiviral treatments for symptomatic COVID-19 outpatients: Systematic review and network meta-analysis.
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Zur M, Peselev T, Yanko S, Rotshild V, and Matok I
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- Adult, Humans, Network Meta-Analysis, Outpatients, Ritonavir adverse effects, Antiviral Agents adverse effects, COVID-19, Hydroxylamines, Cytidine analogs & derivatives, Nitriles, Lactams, Proline, Leucine
- Abstract
Background: Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death., Objectives: To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data., Study Design: This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated., Results: Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects., Conclusions: This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2024
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88. In outpatients with COVID-19 during Omicron variant circulation, molnupiravir and nirmatrelvir-ritonavir improved outcomes.
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Chagla Z
- Subjects
- Humans, Antiviral Agents therapeutic use, COVID-19 Drug Treatment, Ritonavir therapeutic use, SARS-CoV-2, COVID-19, Cytidine analogs & derivatives, Hydroxylamines, Lactams, Leucine, Nitriles, Outpatients, Proline
- Abstract
Source Citation: Sommer I, Ledinger D, Thaler K, et al. Outpatient treatment of confirmed COVID-19: a living, rapid evidence review for the American College of Physicians (version 2). Ann Intern Med. 2023;176:1377-1385. 37722115., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J23-0108.
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- 2024
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89. Regulation mechanism of hydrazine and hydroxylamine in nitrogen removal processes: A Comprehensive review.
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Ma X, Feng ZT, Zhou JM, Sun YJ, and Zhang QQ
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- Hydroxylamine, Oxidation-Reduction, Bioreactors, Nitrification, Hydroxylamines, Hydrazines, Sewage, Denitrification, Nitrogen
- Abstract
As the new fashioned nitrogen removal process, short-cut nitrification and denitrification (SHARON) process, anaerobic ammonium oxidation (anammox) process, completely autotrophic nitrogen removal over nitrite (CANON) process, partial nitrification and anammox (PN/A) process and partial denitrification and anammox (PD/A) process entered into the public eye due to its advantages of high nitrogen removal efficiency (NRE) and low energy consumption. However, the above process also be limited by long-term start-up time, unstable operation, complicated process regulation and so on. As intermediates or by-metabolites of functional microorganisms in above processes, hydroxylamine (NH
2 OH) and hydrazine (N2 H4 ) improved NRE of the above processes by promoting functional enzyme activity, accelerating electron transport efficiency and regulating distribution of microbial communities. Therefore, this review discussed effects of NH2 OH and N2 H4 on stability and NRE of above processes, analyzed regulatory mechanism from functional enzyme activity, electron transport efficiency and microbial community distribution. Finally, the challenges and limitations for nitric oxide (NO) and nitrous oxide (N2 O) produced from regulation of NH2 OH and N2 H4 are discussed. In additional, perspectives on future trends in technology development are proposed., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work. There is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the view of, the manuscript entitled: Regulation Mechanism of Hydrazine and Hydroxylamine in Nitrogen Removal Processes: A Comprehensive Review., (Copyright © 2023 Elsevier Ltd. All rights reserved.)- Published
- 2024
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90. A study survey on molnupiravir treatment in COVID-19 patients at home in Ninh Thuan province, Vietnam.
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Le-Huy T, Balzanelli MG, Thai-Phuong P, Tran Thai T, Nguyen Vu Ngoc H, Tran Phuc L, Le Quoc T, Nguyen Thanh T, Nai Thanh T, Le Van T, Thi Bich LP, Lazzaro R, Distratis P, Dipalma G, Morolla R, Inchingolo AM, Dongiovanni L, Triggiano F, Santacroce L, Del Prete R, Serafini M, Palermo A, Cao Diem Nguyen K, Inchingolo F, and Gargiulo Isacco C
- Subjects
- Humans, Vietnam epidemiology, Longitudinal Studies, Pandemics, COVID-19, Cytidine analogs & derivatives, Hydroxylamines
- Abstract
Objective: Molnupiravir (MOV) is an oral antiviral drug that received use authorization in Vietnam for the treatment of mild COVID-19 (F0). There was a need to develop alternative approaches that allowed patients to access medication, decongest hospitals, clinics, and facilities, and protect people from infection. During the COVID-19 crisis, the Ninh Thuan Health Authorities implemented the home delivery of medication by community health workers. This study conducted in collaboration with two important Italian entities [the Aldo Moro University of Bari City and the 118 Department of Territorial Emergency System (118 SET) of Taranto City] aimed to evaluate the implementation of home delivery F0 treatment package assessing the rate of infection recovering during the coronavirus pandemic in Ninh Thuan province, Vietnam., Patients and Methods: A convergent mixed methods research, based on a longitudinal study with quantitative research and qualitative assessments, evaluated four implementation outcomes: the feasibility, fidelity, coverage, sustainability, and effectiveness of the initiative. Data sources included routinely collected data, a telephonic survey of patients, an analysis of set-up and recurrent costs, as well as descriptive exploratory qualitative and quantitative analysis., Results: After taking the MOV for 5 days, only 35 out of the initial 400 F0 patients remained positive, while 365 patients (91.2%) were negative (CT≥30). Whilst, the successful rate after using the drug during the course accounted for 99.85% and 100% after the entire treatment course, without any death. After 5 days of taking the drug, a positive test result (CT<30) was associated with age group ≥60 (OR=2.7) and comorbidities (OR=3.0) (p<0.05) compared to negative and positive results (CT≥30). Negative factors impacting F0 at home include a shortage of healthcare workers, inadequate supply of thermometers and SpO2 meters, and insufficient financial support for healthcare workers., Conclusions: MOV caused a reduction in the risk of hospitalization or death in mild COVID-19 patients, and molnupiravir was also found to be well tolerated and safe without any major adverse events during the administration period.
- Published
- 2024
- Full Text
- View/download PDF
91. Effect of Cysteine on the Antioxidant Activity of Nitroxyl Radicals during the Oxidation of Methyl Linoleate in Micelles.
- Author
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Tikhonov, I. V., Borodin, L. I., and Pliss, E. M.
- Abstract
Using the model of methyl linoleate (LH) oxidation in micelles, the effect of cysteine on the antioxidant activity of nitroxyl radicals (NR) in micelles is studied. It is found that cysteine enhances the antioxidant effect of NR with a low reduction potential of the oxoammonium cation + nitroxyl radical pair, which is due to the formation of the corresponding hydroxylamines (HA). [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
92. Imidazole Hydrochloride Promoted Synthesis of Nitriles from Aldehydes
- Author
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Suqin Shang, Jianyong Yuan, Yin Wang, Xuetong Wang, Yanwu Li, Xiuyu Zhang, Lingli Li, and Tingshu He
- Subjects
Aldehydes ,Nitrogen ,Nitriles ,Organic Chemistry ,Imidazoles ,Solvents ,Hydrochloric Acid ,Hydroxylamines ,Oxidants ,Biochemistry - Abstract
Background: and objective: As a key pharmacophore, the cyano group widely exists in a variety of biologically active compounds. Besides, nitriles are also valuable intermediates for many common functional groups. In this current work, a new synthesis strategy was developed to obtain nitriles from aldehydes. Methods: Using commercially available aldehydes as raw materials, and hydroxylamine and hydrochloride as nitrogen sources, the corresponding nitrile compounds were successfully synthesized by the one-pot method through the promotion of imidazole hydrochloride. And it was characterized by 1H NMR, 13C NMR, and mass spectrometry. Results: Various reaction conditions were applied in order to find an optimum and convenient procedure for the formation of nitriles. The highest yields (95%) were achieved using sulfolane as a solvent, and imidazole hydrochloride as a promoter. Conclusion: In conclusion, we developed a new synthetic method for nitrile compounds from aldehydes. Twenty seven examples of functionalized nitrile compounds have been synthesized in good to excellent yields. This methodology features that an environmentally benign imidazole hydrochloride replaces transition metal catalysts and oxidants required in conventional strategies to convert aldehydes into nitriles with good functional group tolerability. Further exploration of imidazole hydrochloride is ongoing in our laboratory.
- Published
- 2022
93. Real-world experience with available, outpatient COVID-19 therapies in solid organ transplant recipients during the omicron surge
- Author
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Christopher Radcliffe, Carlo Foppiano Palacios, Marwan M. Azar, Elizabeth Cohen, and Maricar Malinis
- Subjects
Male ,Transplantation ,Ritonavir ,SARS-CoV-2 ,COVID-19 ,Cytidine ,Organ Transplantation ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Hydroxylamines ,Antibodies, Neutralizing ,Antiviral Agents ,Transplant Recipients ,COVID-19 Testing ,Humans ,Immunology and Allergy ,Female ,Pharmacology (medical) - Abstract
The SARS-CoV-2 pandemic continues to place a substantial burden on healthcare systems. Outpatient therapies for mild-to-moderate disease have reduced hospitalizations and deaths in clinical trials, but the real-world effectiveness of monoclonal antibodies and oral antiviral agents in solid organ transplant recipients (SOTR) with coronavirus disease-2019 (COVID-19) is largely uncharacterized. We conducted a single-center, retrospective review of 122 SOTR diagnosed with COVID-19 in the outpatient setting during the Omicron surge to address this knowledge gap. The mean age was 54 years, 57% were males, and 67% were kidney transplant recipients. The mean time from transplant to COVID-19 diagnosis was 75 months. Forty-nine (40%) received molnupiravir, 24 (20%) received sotrovimab, and 1 (0.8%) received nirmatrelvir/ritonavir. No outpatient therapy was administered in 48 (39%). All 122 SOTR had30 days follow-up. Rates of hospitalization within 30 days of initiating therapy for molnupiravir, nirmatrelvir/ritonavir, and sotrovimab were 16% (8/49), 0% (0/1), and 8% (2/24), respectively, compared to 27% (13/48) in patients without outpatient therapy. There were no deaths in those who received any therapy versus 3 (6%) deaths in patients without outpatient therapy (p = .002). Overall, our experience suggests a role for monoclonal antibodies and oral antiviral agents in reducing COVID-19-related morbidity and mortality in SOTR.
- Published
- 2022
94. Reports from Phenikaa University Advance Knowledge in Medicinal Chemistry (Identification of Novel Phenylalanine Derivatives Bearing a Hydroxamic Acid Moiety As Potent Quorum Sensing Inhibitors).
- Abstract
A report from Phenikaa University in Hanoi, Vietnam discusses the identification of novel phenylalanine derivatives bearing a hydroxamic acid moiety as potent quorum sensing inhibitors. These compounds were designed, synthesized, and evaluated for their use as inhibitors of bacterial virulence factors. The research found that six compounds showed good quorum sensing inhibitor properties, with three of them also exhibiting strong anti-biofilm formation and CviR inhibitory activity. The most promising compound for future drug development targeting quorum sensing was identified as 4h. The study concludes that fragment-based drug design is a promising approach for discovering novel quorum-sensing inhibitors. [Extracted from the article]
- Published
- 2024
95. Researchers' Work from Universitat Autonoma de Barcelona Focuses on Ischemia (Histone deacetylase inhibition by suberoylanilide hydroxamic acid during reperfusion promotes multifaceted brain and vascular protection in spontaneously hypertensive...).
- Subjects
HYDROXAMIC acids ,HISTONE deacetylase ,REPERFUSION ,RESEARCH personnel ,CENTRAL nervous system diseases - Abstract
A recent study conducted by researchers at the Universitat Autonoma de Barcelona explores the potential therapeutic benefits of suberoylanilide hydroxamic acid (SAHA) in reducing brain injury caused by ischemia. The study focused on spontaneously hypertensive rats with transient ischemic stroke and found that SAHA administered during early reperfusion demonstrated significant brain and vascular protection. The findings of this study align with previous research in normotensive mice and may contribute to the development of clinical trials assessing the effectiveness and safety of SAHA in treating ischemic stroke. [Extracted from the article]
- Published
- 2024
96. Study Findings from Soran University Update Knowledge in Antimicrobials (Synthesis of Some novel Azomethine Oxide Derived from Aromatic Oximes and their Anti-microbial Studies).
- Abstract
A study conducted at Soran University focused on the synthesis of azomethine oxides, a type of organic compound, and their potential antimicrobial properties. The researchers created several aromatic oximes through the reduction of corresponding aldehydes, which were then used to generate new azomethine oxides through a condensation reaction. The molecular structure of the synthesized compounds was determined using various techniques, and their antimicrobial effectiveness was tested against gram-negative bacteria, gram-positive bacteria, and fungus. The results showed that these azomethine oxides exhibited significant antimicrobial activity compared to standard drugs. For more information, readers can refer to the article "Synthesis of Some novel Azomethine Oxide Derived from Aromatic Oximes and their Anti-microbial Studies" published in ARO-The Scientific Journal of Koya University. [Extracted from the article]
- Published
- 2024
97. Data on Hypertension Described by Researchers at Kunming Medical University (The Hydroxamic Acid Derivative Ypx-c-05 Alleviates Hypertension and Vascular Dysfunction Through the Pi3k/akt/enos Pathway).
- Subjects
HYDROXAMIC acids ,HYPERTENSION ,ACID derivatives ,MEDICAL research personnel ,CARDIOVASCULAR system - Published
- 2024
98. Data on Biocatalysis Described by Researchers at CSIR - Indian Institute of Integrative Medicine (Biocatalytic Synthesis, In Silico Analysis And In Vitro Validation of Hydroxamic Acids Against Histone Deacetylases).
- Abstract
Researchers at the CSIR - Indian Institute of Integrative Medicine in Jammu, India have conducted a study on the synthesis of hydroxamic acids, which have the potential to inhibit metalloenzymes. The researchers aimed to develop a biocatalytic process for synthesizing hydroxamic acids using the resting cells of Bacillus smithii IIIMB2907. Through in silico analysis and in vitro validation, they found that one particular compound showed better interaction with class I histone deacetylases (HDACs) compared to an FDA-approved anti-cancer drug. This study proposes a novel process for synthesizing a potential drug candidate that may act as an HDAC inhibitor. [Extracted from the article]
- Published
- 2024
99. New Findings in Drug Research Described from Charles University of Prague (In Vitro Evaluation of Oxidative Stress Induced By Oxime Reactivators of Acetylcholinesterase In Hepg2 Cells).
- Abstract
A recent study conducted at Charles University in Prague explored the potential oxidative stress induced by oxime reactivators of acetylcholinesterase (AChE) in HepG2 cells. Oxime reactivators are used as antidotes for poisoning by nerve agents and pesticides. The study found that the structure of oximes plays a critical role in inducing oxidative stress, and this relationship does not correlate with their cytotoxicity. The researchers concluded that oxidative stress should not be disregarded as a potential contributor to the side effects associated with oximes. [Extracted from the article]
- Published
- 2024
100. Reports Outline Life Science Study Findings from National Agriculture and Food Research Organization [Diversity of the Hydroxylamine Oxidoreductase (Hao) Gene and Its Enzyme Active Site In Agricultural Field Soils].
- Abstract
A recent study conducted by researchers at the National Agriculture and Food Research Organization in Ibaraki, Japan, explored the diversity of the hydroxylamine oxidoreductase (HAO) gene and its enzyme active site in agricultural field soils. The study found that the diversity of the HAO gene in beta-proteobacterial ammonia-oxidizing bacteria and complete ammonia-oxidizing bacteria was influenced by fertilizer treatment and field type, respectively. The researchers concluded that this study provides valuable insights into HAO gene diversity in agricultural soils, which can aid in the development of inhibitors for nitrification in agricultural soils. [Extracted from the article]
- Published
- 2024
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