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Background and purpose: Sodium channel blockers (SCBs) have traditionally been utilized as anti‐seizure medications by primarily targeting the inactivation process. In a drug discovery project aiming at finding potential anticonvulsants, we have identified arbidol, originally an antiviral drug, as a potent SCB. In order to evaluate its anticonvulsant potential, we have thoroughly examined its biophysical properties as well as its effects on animal seizure models. Experimental approach: Patch clamp recording was used to investigate the electrophysiological properties of arbidol, as well as the binding and unbinding kinetics of arbidol, carbamazepine and lacosamide. Furthermore, we evaluated the anticonvulsant effects of arbidol using three different seizure models in male mice. Key results: Arbidol effectively suppressed neuronal epileptiform activity by blocking sodium channels. Arbidol demonstrated a distinct mode of action by interacting with both the fast and slow inactivation of Nav1.2 channels compared with carbamazepine and lacosamide. A kinetic study suggested that the binding and unbinding rates might be associated with the specific characteristics of these three drugs. Arbidol targeted the classical binding site of local anaesthetics, effectively inhibited the gain‐of‐function effects of Nav1.2 epileptic mutations and exhibited varying degrees of anticonvulsant effects in the maximal electroshock model and subcutaneous pentylenetetrazol model but had no effect in the pilocarpine‐induced status epilepticus model. Conclusions and implications: Arbidol shows promising potential as an anticonvulsant agent, providing a unique mode of action that sets it apart from existing SCBs. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts have sought to identify small-molecule antivirals with various mechanisms of action. Here, we aim to review research progress on small-molecule viral entry and fusion inhibitors that directly bind to the SARS-CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in in vitro SARS-CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small-molecule binding sites on Spike, it was unclear what the specific mechanism of action was or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor-binding domain (RBD) or N-terminal domain (NTD) and disrupt the S1 receptor-binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most substitutions to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved, with only a few observed substitutions in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over recent VOC mutant strains and/or greater broad-spectrum antiviral activity for other more distantly related coronaviruses. [ABSTRACT FROM AUTHOR]

Antiviral therapies are integral in the fight against SARS‐CoV‐2 (i.e. severe acute respiratory syndrome coronavirus 2), the causative agent of COVID‐19. Antiviral therapeutics can be divided into categories based on how they combat the virus, including viral entry into the host cell, viral replication, protein trafficking, post‐translational processing, and immune response regulation. Drugs that target how the virus enters the cell include: Evusheld, REGEN‐COV, bamlanivimab and etesevimab, bebtelovimab, sotrovimab, Arbidol, nitazoxanide, and chloroquine. Drugs that prevent the virus from replicating include: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, and Kaletra. Drugs that interfere with protein trafficking and post‐translational processing include nitazoxanide and ivermectin. Lastly, drugs that target immune response regulation include interferons and the use of anti‐inflammatory drugs such as dexamethasone. Antiviral therapies offer an alternative solution for those unable or unwilling to be vaccinated and are a vital weapon in the battle against the global pandemic. Learning more about these therapies helps raise awareness in the general population about the options available to them with respect to aiding in the reduction of the severity of COVID‐19 infection. In this 'A Guide To' article, we provide an in‐depth insight into the development of antiviral therapeutics against SARS‐CoV‐2 and their ability to help fight COVID‐19. [ABSTRACT FROM AUTHOR]

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results related to molecular docking and modeling of the structure–activity relationship (SAR) of a newly reported series of Clofazimine derivatives support the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure–sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronaviruses such as SARS-CoV, MERS, hCoV-229E, and hCoV-OC43. [ABSTRACT FROM AUTHOR]

As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug–drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 μL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 μM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was noncompetitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice. [ABSTRACT FROM AUTHOR]

An approach to the highly sensitive and selective determination of the bromine-containing antiviral drug umifenovir (Arbidol) and its metabolites in natural and waste water, activated sludge, and bottom sediments by chromatography-mass spectrometry based on a combination of two techniques– inductively coupled plasma mass spectrometry (ICP MS) and electrospray ionization high-resolution mass spectrometry (ESI HRMS) is developed. Reversed-phase chromatographic separation and detection based on ESI HRMS provide the reliable detection and identification of analytes in complex matrices, while the use of ICP-MS with 79Br signal detection makes it possible to exclude matrix effects and use a single analytical standard for quantitative analysis. The use of solid-phase extraction and pressurized liquid extraction as sample preparation methods made it possible to achieve limits of detection at a level of 0.2 ng/L and 2 µg/kg for liquid and solid samples, respectively. The developed approach was successfully tested in the analysis of real samples. It is shown that the concentrations of analytes in urban wastewaters are in the range 4.4–260 ng/L. The highest concentration (up to 3.7 mg/kg) is characteristic of activated sludge, which acts as an effective sorbent for umifenovir and its transformation products. [ABSTRACT FROM AUTHOR]

Human coronavirus OC43 (HCoV‐OC43) often causes common cold and is able to neuroinvasive, but it can also induce lower respiratory tract infections (LRTI) especially in children and the elderly adults with underlying diseases. HCoV‐OC43 infections currently have no approved antiviral treatment. Arbidol (ARB) is a broad‐spectrum antiviral and is an antiviral medication for the treatment of influenza used in Russia and China. Due to its multiple mechanisms of action, such as inhibition of viral fusion and entry, immunomodulation, and modulation of host cell signaling pathways, ARB has the potential to be an effective treatment option for viral infections. Therefore, the study aims to investigate the activities of ARB against HCoV‐OC43 infections. Suckling mice were infected with HCoV‐OC43 and treated with ARB (50, 25 and 12.5 mg/kg/d) by gavage once daily for 4 days. the survival rates and body weight were recorded, the viral titer was measured by real‐time quantitative polymerase chain reaction, cytokine levels were measured by Bio‐Plex assays. Histopathological changes of the lungs and brain were analyzed. Our results show ARB increased the survival rate, reduced viral copy numbers in the lung, mitigated pro‐inflammatory cytokine production, and improved brain and lung histopathology significantly without any significant toxicity or side effects in vivo. Our results suggest ARB could be a promising approach for the prevention and treatment of HCoV‐OC43 while further studies are needed to address these possibilities and the underlying mechanism. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts have sought to identify small-molecule antivirals with various mechanisms of action. Here, we aim to review research progress on small-molecule viral entry and fusion inhibitors that directly bind to the SARS-CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in in vitro SARS-CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small-molecule binding sites on Spike, it was unclear what the specific mechanism of action was or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor-binding domain (RBD) or N-terminal domain (NTD) and disrupt the S1 receptor-binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most substitutions to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved, with only a few observed substitutions in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over recent VOC mutant strains and/or greater broad-spectrum antiviral activity for other more distantly related coronaviruses.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs that have been repurposed for the treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule bindings to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 Spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and its derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest-quality SPR data for binding with S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results related to molecular docking and modeling of the structure–activity relationship (SAR) of a newly reported series of Clofazimine derivatives support the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure–sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronaviruses such as SARS-CoV, MERS, hCoV-229E, and hCoV-OC43.

Background: High morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem. Methods: Two independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022. Results: Based on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus‐targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host‐targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian‐made indole‐derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion. Conclusion: ARB is a broad‐spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high‐quality clinical studies are required to establish the efficacy and safety of ARB. [ABSTRACT FROM AUTHOR]

Abstract Background High morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem. Methods Two independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022. Results Based on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus‐targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host‐targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian‐made indole‐derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion. Conclusion ARB is a broad‐spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high‐quality clinical studies are required to establish the efficacy and safety of ARB.

Background: SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. Methodology: We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). Results: Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between − 10.7 to − 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (−6.6 to −5.1 kcal/mol), favipiravir (−5.5 to −4.5 kcal/mol), hydroxychloroquine (−6.5 to −5.1 kcal/mol), and remedesivir (−8.0 to −5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). Conclusion: Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency.

Understanding of the nucleation process's fundamental principles in saturated solutions is an urgent task. To do this task, it is necessary to control the formation of polymorphic forms of biologically active compounds. In certain cases, a compound can exist in a single polymorphic form, but have several solvates which can appear in different crystal forms, depending on the medium and conditions of formation, and show different pharmaceutical activity. In the present paper, we report on the analysis of Arbidol conformational preferences in two solvents of different polarities—deuterated chloroform and dimethyl sulfoxide—at 25 °C, using the 2D NOESY method. The Arbidol molecule has various solvate forms depending on the molecular conformation. The method based on the nuclear Overhauser effect spectroscopy was shown to be efficient in the analysis of complex heterocyclic compounds possessing conformation-dependent pseudo-polymorphism. It is one of the types of polymorphism observed in compounds forming crystal solvates. Combined use of NMR methods and X-ray data allowed determining of conformer populations of Arbidol in CDCl3 and DMSO-d6 which were found to be 8/92% and 37/63%, respectively. The preferred conformation in solution is the same that appears in stable crystal solvates of Arbidol. [ABSTRACT FROM AUTHOR]

Influenza is a serious public health problem. The ability of influenza virus to change upon replication is the most serious issue for practical medicine and virology, which can fundamentally alter virus biological properties, such as infectivity and virulence. The high mutational variability of influenza viruses can contribute to rapidly emerging drug resistance. Therefore, the study of antiviral drug sensitivity among influenza viruses is necessary to justify proper drug use for treatment and prevention of influenza infection. The aim of the study was to examine antiviral drug susceptibility of influenza A/H1N1 and B virus strains isolated from various regions of Kazakhstan in the years 2018–2019. Materials and methods. The susceptibility analysis of 20 strains of influenza A/H1N1 and B viruses was carried out by using chemotherapeutic agents including Remantadine, Tamiflu, Arbidol, and Ingavirin. Viruses were cultured in the allantoic cavity of developing 10-day-old chicken embryos for 48 hours at 36оC. The hemagglutinating activity was determined according to the standard method on 96-well plates using 0.75% chicken red blood cell suspension; the infectivity was calculated by the Reed–Muench method. The susceptibility of virus strains to different concentrations of antiviral drugs was evaluated by the level of virus reproductive suppression of 100 lg EID50/0.2 ml in chicken embryos. Statistical analysis was performed using Microsoft Office Excel 2010 software. Results. A study of susceptibility to chemotherapeutic agents demonstrated heterogeneity of influenza A and B virus population isolated in Kazakhstan during the 2018–2019 period. The susceptibility to tamiflu was found in all Kazakhstan strains of influenza A/H1N1 virus and three type B strains (inhibitory concentration was 0.44–25.38 μg/mL). The reproduction of most viruses was effectively inhibited by Tamiflu at a concentration of 0.68–3.23 μg/mL. The inhibitory concentration for three strains of A/H1N1 virus was 7.23–25.38 μg/mL. Remantadine inhibited reproduction of viruses at higher doses (12.60–25.55 μg /mL). All investigated viruses were resistant to Arbidol and Ingavirin. A single type B influenza virus strain was found to be weakly susceptible to Ingavirin. Conclusion. The heterogeneity of influenza virus population in susceptibility to antiviral drugs suggest a need for constant epidemiological surveillance in order to identify drug-resistant variants.

Abstract Objective To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID‐19 treatment. Methods A literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle–Ottawa scale were used to assess the quality of included studies. Meta‐analysis was performed using RevMan 5.3. Results Sixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non‐antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR‐PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78–1.14) and Day 14 (RR: 1.10; 95% CI: 0.96–1.25), and PCR negative conversion time (PCR‐NCT; mean difference [MD]: 0.74; 95% CI: −0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06–4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05). Conclusion The present meta‐analysis showed no significant benefit of using arbidol compared with non‐antiviral treatment or other therapeutic agents against COVID‐19 disease. High‐quality studies are needed to establish the efficacy and safety of arbidol for COVID‐19.

Dengue virus infection, caused by a single positive-stranded RNA virus from the Flaviviridae family, represents a significant public health challenge in tropical and subtropical regions. This virus has four serotypes (DENV-1, 2, 3, and 4), primarily transmitted by Aedes mosquitoes. Despite extensive research, effective antiviral treatments and vaccines remain elusive due to the viral diversity and the complex mechanisms such as antibody-dependent enhancement (ADE). In the current study, NS1-positive serum samples from dengue cases in Pakistan (2023-2024), were analyzed to determine the predominant serotype and characterize the envelope (E) gene for further exploration of antiviral targets. Out of 100 samples, 63 (63%) tested positive for DENV-2, indicating its predominance during this period, while two samples showed mixed infections with DENV-2 and DENV-3. The envelope gene was successfully amplified using nested PCR, validated through gel electrophoresis and sanger sequencing. Phylogenetic analysis revealed high similarity of the DENV-2 isolates to strains from China and India. Computational modeling of the envelope protein structure identified potential antiviral binding sites and further molecular docking studies suggested that specific antiviral compounds like Arbidol and Quercetin can inhibit early steps in viral infection. Additionally, BepiPred-3.0 predicted several B-cell epitopes, which could be useful for vaccine development. These findings enhance our understanding of dengue epidemiology in Pakistan and contribute to the development of targeted antiviral therapies, potentially informing future vaccination strategies and outbreak management., 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.)

SARS-CoV-2, an emerged strain of corona virus family became almost serious health concern worldwide. Despite vaccines availability, reports suggest the occurrence of SARS-CoV-2 infection even in a vaccinated population. With frequent evolution and expected multiple COVID-19 waves, improved preventive, diagnostic, and treatment measures are required. In recent times, phytochemicals have gained attention due to their therapeutic characteristics and are suggested as alternative and complementary treatments for infectious diseases. This present study aimed to identify potential inhibitors against reported protein targets of SARS-CoV-2. We computationally investigated potential SARS-CoV-2 protein targets from the literature and collected druggable phytochemicals from Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) database. Further, we implemented a systematic workflow of molecular docking, dynamic simulations and generalized born surface area free-energy calculations (MM-GBSA). Extensive literature search and assessment of 1508 articles identifies 13 potential SARS-CoV-2 protein targets. We screened 501 druggable phytochemicals with proven biological activities. Analysis of 6513(501 *13) docked phytochemicals complex, 26 were efficient against SARS-CoV-2. Amongst, 4,8-dihydroxysesamin and arboreal from Gmelina arborea were ranked potential against most of the targets with binding energy ranging between − 10.7 to − 8.2 kcal/mol. Additionally, comparative docking with known drugs such as arbidol (−6.6 to −5.1 kcal/mol), favipiravir (−5.5 to −4.5 kcal/mol), hydroxychloroquine (−6.5 to −5.1 kcal/mol), and remedesivir (−8.0 to −5.3 kcal/mol) revealed equal/less affinity than 4,8-dihydroxysesamin and arboreal. Interestingly, the nucleocapsid target was found commonly inhibited by 4,8-dihydroxysesamin and arboreal. Molecular dynamic simulation and Molecular mechanics generalized born surface area (MM-GBSA)calculations reflect that both the compounds possess high inhibiting potential against SARS-CoV-2 including the recently emerged Omicron variant (B.1.1.529). Overall our study imparts the usage of phytochemicals as antiviral agents for SARS-CoV-2 infection. Additional in vitro and in vivo testing of these phytochemicals is required to confirm their potency. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has resulted in more than 524 million cases and 6 million deaths worldwide. Various drug interventions targeting multiple stages of COVID-19 pathogenesis can significantly reduce infection-related mortality. The current within-host mathematical modeling study addresses the optimal drug regimen and efficacy of combination therapies in the treatment of COVID-19. The drugs/interventions considered include Arbidol, Remdesivir, Interferon (INF) and Lopinavir/Ritonavir. It is concluded that these drugs, when administered singly or in combination, reduce the number of infected cells and viral load. Four scenarios dealing with the administration of a single drug, two drugs, three drugs and all four are discussed. In all these scenarios, the optimal drug regimen is proposed based on two methods. In the first method, these medical interventions are modeled as control interventions and a corresponding objective function and optimal control problem are formulated. In this framework, the optimal drug regimen is derived. Later, using the comparative effectiveness method, the optimal drug regimen is derived based on the basic reproduction number and viral load. The average number of infected cells and viral load decreased the most when all four drugs were used together. On the other hand, the average number of susceptible cells decreased the most when Arbidol was administered alone. The basic reproduction number and viral load decreased the most when all four interventions were used together, confirming the previously obtained finding of the optimal control problem. The results of this study can help physicians make decisions about the treatment of the life-threatening COVID-19 infection. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia. Methods This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People’s Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir–ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness. Results Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value

Viral nervous necrosis (VNN) caused by nervous necrosis virus (NNV) poses a significant threat to the global aquaculture industry, leading to substantial economic losses. In this study, we evaluated the anti-NNV activity of arbidol both in vitro and in vivo. Treatment with arbidol at a concentration of 10.48 μM effectively inhibited NNV-induced cytopathic effects in GF-1 cells, and the half-maximal inhibitory concentration (IC 50) of arbidol against NNV was determined to be 7.915 μM. To improve drug delivery to the central nervous system, the primary site of NNV infection, we developed positively charged mesoporous silica nanocarriers (CMSNs) loaded with arbidol (CMSNs-ARB). Compared to unmodified mesoporous silica nanocarriers, CMSNs exhibited significantly higher uptake in GF-1 cells and zebrafish brains, indicating their potential to cross the blood-brain barrier (BBB) and deliver drugs more efficiently. In vivo experiments revealed that arbidol administration improved the survival rate of juvenile fish infected with NNV. Additionally, the use of CMSNs as a drug carrier further enhanced the larval survival rate by 13 % compared to the arbidol-only treatment group. These results demonstrate the potent anti-NNV activity of arbidol and highlight the potential of CMSNs as an effective drug delivery system to control fish viral diseases in aquaculture. • Arbidol shows a strong anti-NNV activity both in vitro and in vivo. • An efficient drug delivery system was constructed, named as PMSNs-ARB. • PMSNs-ARB can be internalized in GF-1 cells and barin of zebrafish by soaking. • Arbidol delivery with PMSNs has a positive impact on NNV therapy. [ABSTRACT FROM AUTHOR]

Increasing antivirals in surface water caused by their excessive consumption pose serious threats to aquatic organisms. Our recent research found that the input of antiviral drug arbidol to algal bloom water can induce acute toxicity to the growth and metabolism of Microcystis aeruginosa , resulting in growth inhibition, as well as decrease in chlorophyll and ATP contents. However, the toxic mechanisms involved remained obscure, which were further investigated through transcriptomic analysis in this study. The results indicated that 885–1248 genes in algae were differentially expressed after exposure to 0.01–10.0 mg/L of arbidol, with the majority being down-regulated. Analysis of commonly down-regulated genes found that the cellular response to oxidative stress and damaged DNA bonding were affected, implying that the stress defense system and DNA repair function of algae might be damaged. The down-regulation of genes in porphyrin metabolism, photosynthesis, carbon fixation, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation might inhibit chlorophyll synthesis, photosynthesis, and ATP supply, thereby hindering the growth and metabolism of algae. Moreover, the down-regulation of genes related to nucleotide metabolism and DNA replication might influence the reproduction of algae. These findings provided effective strategies to elucidate toxic mechanisms of contaminants on algae in algal bloom water. [Display omitted] • Toxic mechanisms of ARB on M. aeruginosa were investigated by transcriptomics. • The oxidative stress system of algae was damaged under all concentrations of ARB. • ARB suppressed the genes chlH , chlE , chlN , and bciB in chlorophyll synthesis. • The photosynthesis and ATP production in M. aeruginosa were suppressed by ARB. • ARB down-regulated the genes dnaE , dnaX , SSB , and ligA related to DNA replication. [ABSTRACT FROM AUTHOR]

Deep eutectic solvents are a new generation of green solvents composed of hydrogen bond acceptors and donors. However, when used as extractants in liquid–liquid separation, they are difficult to recycle and easy to lose. In order to solve these problems, herein, immobilized hydrogen bond acceptor adsorbent material was prepared for the separation and enrichment of antiviral drug arbidol from seven kinds of environmental water samples by in situ formation of hydrophobic deep eutectic solvents. The structure, morphology and thermal stability of the adsorbents were characterized, the separation and enrichment conditions for the targeted analyte were optimized, and the adsorption thermodynamics and kinetics were investigated. It was found that the adsorbent material could effectively enrich trace arbidol with the recovery more than 95% at the concentration above 7.5 ng/mL, and the enrichment factor was as high as 634.7. Coexisting substances, such as NaCl, KCl, CaCl2 and MgCl2, did not interfere with the adsorption of arbidol, even if their concentration was high, up to 1.0 mol/L, and the relative recovery for real samples was in the range from 92.5% to 100.3%. Furthermore, the immobilized hydrogen bond acceptor could be recycled and reused, and the recovery of arbidol was still above 95% after 12 adsorption–desorption cycles. The mechanism study demonstrates that the synergistic effect of hydrogen bonding and π-π stacking is the primary factor for the high adsorption efficiency. [ABSTRACT FROM AUTHOR]

Arbidol is a kind of non-nucleoside broad-spectrum antiviral drugs, which plays an antiviral role mainly by inhibiting the entry of virus into cells and regulating immunity. A large number of experiments have confirmed the antiviral activity of arbidol against a variety of viruses, including DNA and RNA viruses, enveloped and non-enveloped viruses. In China, arbidol is mainly used for the treatment of upper respiratory tract infection caused by influenza A and B virus. After the outbreak of COVID-19 pandemic, the results of in vitro and in vivo experiments confirmed that arbidol has significant inhibitory effects on SARS-CoV-2, and the use of arbidol can improve the clinical outcomes of patients, yet there are also reports shows that arbidol has no definite curative efficacy. As a kind of potentially effective antiviral drugs, arbidol still needs a lot of clinical practice confirmation. [ABSTRACT FROM AUTHOR]

Objectives: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID‐19) using a meta‐analysis method. Methods: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID‐19. Meta‐analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID‐19. Results: The results of the systematic review indicated that Arbidol had a higher positive‐to‐negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleic acid on Day 7 (p = 0.03), a higher positive‐to‐negative conversion rate of SARS‐CoV‐2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. Conclusions: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID‐19. However, due to the small number of included studies and the number of patients, high‐quality multicenter large‐sample randomized double‐blind controlled trials are still needed for verification. [ABSTRACT FROM AUTHOR]

Sulfur‐containing indoles are widely studied against different biological targets. Among several potential drug candidates, seven molecules of this class are in the current market and a few of them are either in pipeline or in different stages of clinical trials. Particularly, arylthioindoles or indolylarylsulfones (IAS) received great attention by medicinal chemists due to their pharmokinetic profiles and wide spectrum of biological activities like antiviral, anticancer, cardiovascular, and antibacterial properties. This review summarizes the developmental process, synthesis and structure activity relationship (SAR) around arylthioindole/indolylaryl sulfone scaffolds for antiviral/anti‐HIV non‐nucleoside reverse transcriptase inhibitor (NNRTIs) activities. It also offers perspective for further development of 3‐indolylarylsulfones as an anti‐viral agent including their potential against novel COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Due to the high mutation rate of influenza virus and the rapid increase of drug resistance, it is imperative to discover host-targeting antiviral agents with broadspectrum antiviral activity. Considering the discrepancy between the urgent demand of antiviral drugs during an influenza pandemic and the long-term process of drug discovery and development, it is feasible to explore host-based antiviral agents and strategies from antiviral drugs on the market. In the current study, the antiviral mechanism of arbidol (ARB), a broad-spectrum antiviral drug with potent activity at early stages of viral replication, was investigated from the aspect of hemagglutinin (HA) receptors of host cells. N-glycans that act as the potential binding receptors of HA on 16-human bronchial epithelial (16-HBE) cells were comprehensively profiled for the first time by using an indepth glycomic approach based on TiO2-PGC chip-Q-TOF MS. Their relative levels upon the treatment of ARB and virus were carefully examined by employing an ultra-high sensitive qualitative method based on Chip LC-QQQ MS, showing that ARB treatment led to significant and extensive decrease of sialic acid (SA)-linked N-glycans (SA receptors), and thereby impaired the virus utilization on SA receptors for rolling and entry. The SA-decreasing effect of ARB was demonstrated to result from its inhibitory effect on sialyltransferases (ST), ST3GAL4 and ST6GAL1 of 16-HBE cells. Silence of STs, natural ST inhibitors, as well as sialidase treatment of 16-HBE cells, resulted in similar potent antiviral activity, whereas ST-inducing agent led to the diminished antiviral effect of ARB. These observations collectively suggesting the involvement of ST inhibition in the antiviral effect of ARB. [ABSTRACT FROM AUTHOR]

Abstract Background Treatment of patients with COVID-19 has included supportive care to mainly relief symptoms of the disease. Although World Health Organization (WHO) has not recommended any effective treatments for COVID-19, there are some reports about use of antiviral drugs. The aim of this study is to determine the effect of Arbidol (ARB) on COVID-19 disease. Methods Using an open-label randomized controlled trial, we examined the efficacy of ARB in patients with COVID-19 in a teaching hospital. One hundred eligible patients with diagnosis of COVID-19 were recruited in the study and assigned randomly to two groups of either hydroxychloroquine followed by KALETRA (Lopinavir/ritonavir) or hydroxychloroquine followed by ARB. The primary outcome was hospitalization duration and clinical improvement 7 days after admission. The criteria of improvement were relief of cough, dyspnea, and fever. Time to relief from fever was also assessed across the two groups. Without any dropouts, 100 patients were entered into the study for the final analysis at significance level of 0.05. Results The mean age of patients was 56.6 (17.8) years and 56.2 (14.8) years in ARB and KALETRA groups, respectively. Majority of patients were male across two groups (66 and 54%). The duration of hospitalization in ARB group was significantly less than KALETRA arm (7.2 versus 9.6 days; P = 0.02). Time to relief fever was almost similar across two groups (2.7 versus 3.1 days in ARB and KALETRA arms, respectively). Peripheral oxygen saturation rate was significantly different after 7 days of admission across two groups (94% versus 92% in ARB and KALETRA groups respectively) (P = 0.02). Based on multiple linear regression analysis, IHD, Na level, and oxygen saturation at the time of admission and type of therapy were the independent adjusted variables that determined the duration of hospitalization in patients with COVID-19. Conclusion Our findings showed that Arbidol, compared to KALETRA, significantly contributes to clinical and laboratory improvements, including peripheral oxygen saturation, requiring ICU admissions, duration of hospitalization, chest CT involvements, WBC, and ESR. We suggest further studies on ARB against COVID-19 using larger sample size and multicenter design. Trial registration IRCT20180725040596N2 on 18 April 2020.

Objective: To provide the latest evidence for the efficacy and safety of arbidol (umifenovir) in COVID-19 treatment. Methods: A literature systematic search was carried out in PubMed, Cochrane Library, Embase, and medRxiv up to May 2021. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of included studies. Meta-analysis was performed using RevMan 5.3. Results: Sixteen studies were met the inclusion criteria. No significant difference was observed between arbidol and non-antiviral treatment groups neither for primary outcomes, including the negative rate of PCR (NR-PCR) on Day 7 (risk ratio [RR]: 0.94; 95% confidence interval (CI): 0.78-1.14) and Day 14 (RR: 1.10; 95% CI: 0.96-1.25), and PCR negative conversion time (PCRNCT; mean difference [MD]: 0.74; 95% CI: -0.87 to 2.34), nor secondary outcomes (p > .05). However, arbidol was associated with higher adverse events (RR: 2.24; 95% CI: 1.06-4.73). Compared with lopinavir/ritonavir, arbidol showed better efficacy for primary outcomes (p < .05). Adding arbidol to lopinavir/ritonavir also led to better efficacy in terms of NR-PCR on Day 7 and PCR-NCT (p < .05). There was no significant difference between arbidol and chloroquine in primary outcomes (p > .05). No remarkable therapeutic effect was observed between arbidol and other agents (p > .05). Conclusion: The present meta-analysis showed no significant benefit of using arbidol compared with non-antiviral treatment or other therapeutic agents against COVID-19 disease. High-quality studies are needed to establish the efficacy and safety of arbidol for COVID-19. [ABSTRACT FROM AUTHOR]

Abstract Objective We aimed to describe the features of 220 nonemergency (mild or common type) COVID-19 patients from a shelter hospital, as well as evaluate the efficiency of antiviral drug, Arbidol in their disease progressions. Methods Basic clinical characteristics were described and the efficacy of Arbidol was evaluated based on gender, age, maximum body temperature of the patients. Results Basically, males had a higher risk of fever and more onset symptoms than females. Arbidol could accelerate fever recovery and viral clearance in respiratory specimens, particularly in males. Arbidol also contributed to shorter hospital stay without obvious adverse reactions. Conclusions In the retrospective COVID-19 cohort, gender was one of the important factors affecting patient's conditions. Arbidol showed several beneficial effects in these patients, especially in males. This study brought more researches enlightenment in understanding the emerging infectious disease.

The data оп cytotoxicity and antiviral activity of commercial antivirals, such as Remantadine, Oseltamivir, Arbidol and Ribavirin in the MDCK cell culture infected with highly pathogenic (H5N1) and pandemic 2009 (H1N1) influenza A viruses are presented. The study of the antiviral activity of antivirals in the MDCK cells culture demonstrated that Arbidol, Rimantadine and Ribavirin efficiently inhibited reproduction of the highly pathogenic H5N1 influenza viruses isolated from sick birds. Arbidol and Oseltamivir carboxylate selectively inhibited reproduction of the pandemic 2009 H1N1 influenza A viruses with changed specificity to the cell receptors, causing severe influenza in men, while remantadine had no effect on their reproduction.

Efficacy of arbidol and ridostin in cupping postvaccinal complications due to variolation was studied by the clinico-virological, hematological and biochemical indices and it was shown that arbidol was efficient in cupping development of dermal complications, lowered the severity of the postvaccinal reaction and stimulated the cellular and humoral immune response. Ridostin, a high molecular interferon inductor, was highly efficient in cupping all the forms of the postvaccinal complications, including the neurological and cutaneous ones.

The experiment on guinea pigs shows that Ingavirin, when administered orally in a single dose of 15 mg/kg on the 4 th day after vaccination with TEOVac, reduces accumulation of vaccine virus in organs and tissues of animals without affecting the immunogenicity of the vaccine. This efficacy is less pronounced when it is used together with TEOVac. When administered three times orally on days 6, 7, and 8 after immunization, Ingavirin reduces the level of vaccine virus in the blood, liver, and oral mucosa by a factor of 2 or more. Ingavirin is almost as effective as Arbidol, but less effective than Ridostin. These data indirectly indicate the possibility of using ingavirin along with ridostin to prevent post-vaccination reactions during immunization with TEOVac, and also give grounds to consider ridostin, ingavirin, and arbidol as a means of treating post-vaccination reactions.

The therapeutic efficacy of Viferon® (suppositories of human recombinant interferon alfa-2) was investigated in a double-blind controlled study with the use of Arbidol® as a reference drug in the treatment of patients with influenza. Viferon® and Arbidol® lowered the signs of the fever, intoxication, catarrh and the disease as the whole.

Biological properties of influenza viruses A (H1N1), that were the cause of the infection in humans in April - May 2009, and the action of the Russian antivirals on their reproduction were studied in vitro. The nucleotide sequence in the viruses was determined and followed by detection of the mutations responsible for resistance to the antiinfluenza drugs. The experiments showned that arbidol and ribavirin had a selective inhibitory action on reproduction of the viruses in the MDCK cell culture while rimantadine had no affect on their reproduction. The data were confirmed by the results of the genome analysis in influenza viruses A/California/04/2009(H1N1), A/California/07/2009(H1N1) and A/Moscow/01/2009(H1N1)swl, that revealed no replacements defining the resistance to arbidol while the viruses contained a mutation in position 31 of М2 protein, responsible for the resistance to adamantans.

Understanding of the nucleation process’s fundamental principles in saturated solutions is an urgent task. To do this task, it is necessary to control the formation of polymorphic forms of biologically active compounds. In certain cases, a compound can exist in a single polymorphic form, but have several solvates which can appear in different crystal forms, depending on the medium and conditions of formation, and show different pharmaceutical activity. In the present paper, we report on the analysis of Arbidol conformational preferences in two solvents of different polarities—deuterated chloroform and dimethyl sulfoxide—at 25 °C, using the 2D NOESY method. The Arbidol molecule has various solvate forms depending on the molecular conformation. The method based on the nuclear Overhauser effect spectroscopy was shown to be efficient in the analysis of complex heterocyclic compounds possessing conformation-dependent pseudo-polymorphism. It is one of the types of polymorphism observed in compounds forming crystal solvates. Combined use of NMR methods and X-ray data allowed determining of conformer populations of Arbidol in CDCl3 and DMSO-d6 which were found to be 8/92% and 37/63%, respectively. The preferred conformation in solution is the same that appears in stable crystal solvates of Arbidol.

Introduction. The emergence of influenza virus strains with drug resistance to antiviral drugs requires finding new compounds, potential direct-acting inhibitors. Аdamantane compounds drugs used since the 1960s have lost their activity the resulting due to resistance. Only neuraminidase inhibitors such as zanamivir and oseltamivir have been approved by WHO for influenza treatment. The Russian pharmaceutical drug Arbidol (Umifenovirum) is actively used in Russia. This drug is used to treat influenza in Russia, China and most post-Soviet republics. This work presents a new derivative of aminoadamantane - dichlorohydrate L-histidyl-1-adamantayl ethylamine (2HCl*H-His-Rim), which showed a high level of inhibition of strains of influenza virus A in vitro. Objectives. Comparison of antiviral properties of the new synthetic low-molecular inhibitor of influenza A virus replication and Arbidol drug pharmacy. Methods. The compound 2HCl*H-His-Rim was obtained by classical peptide synthesis methods. It was identified by methods of mass spectrometry, infrared spectroscopy (IR) and nuclear magnetic resonance spectroscopy (NMR). Its antiviral properties have been studied in vitro for monolayer of cells Vero-E6 infected with a high-virulent strain of A/duck/Novosibirsk/56/06 (H5N1) influenza virus at various injection schemes of the investigated compounds. The results. The antiviral activity of the 2HCl*H-His-Rim compound against the highly pathogenic strain of the influenza A/H5N1 virus was slightly higher than for the known pharmacy drug arbidol. Discussion. The difference in antiviral activity of these two compounds is explained by different mechanisms of action on the viral particle. Conclusion. The 2HCl*H-His-Rim compound can be recommended as a candidate for preclinical and clinical trials in order to obtain an etiotropic antiviral drug based on it, due to its high efficacy and economic and synthetic availability. The synthetic compound 2HCl*H-His-Rim acts on influenza A virus variants resistant to Rimantadine and Amantadine.

The sensitive and rapid stability‐indicating green reversed‐phase (RP)/routine normal‐phase (NP) high‐performance thin‐layer chromatography (HPTLC) technique has been established for the analysis of arbidol (ADL) from green analytical chemistry viewpoint. The green reversed‐phase analysis of ADL was carried out using RP‐18 silica gel 60 F254S plates. The mobile phase for the green reversed‐phase technique was ethanol/water/ammonia (80:10:10, vol/vol/vol). The routine normal‐phase analysis of ADL was performed using NP‐18 silica gel 60 F254S plates. The mobile phase for the routine normal‐phase technique was hexane/acetone/ammonia (50:45:5, vol/vol/vol). The detection of ADL was performed at 317 nm for both of the techniques. The linearity ranges for the green reversed‐phase and routine normal‐phase techniques were recorded as 40–800 ng/band and 100–600 ng/band, respectively. The proposed reversed‐phase HPTLC technique was also found to be stability‐indicating for the quantification of ADL in the presence of impurities/degradation products. The AGREE scores for green reversed‐phase HPTLC and routine normal‐phase HPTLC techniques were obtained as 0.86 and 0.49, respectively, suggesting the excellent greenness for reversed‐phase HPTLC technique compared with routine normal‐phase HPTLC technique. Overall, the green reversed‐phase HPTLC technique was found to be superior over routine normal‐phase HPTLC technique for the detection of ADL. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia. Methods: This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People's Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir–ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness. Results: Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084–0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15–0.58, p = 0.0005). The use of lopinavir–itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of − 5.2 days (IQR − 3.0 to − 7.5, p = 4e−06) compared with the control group. Conclusion: Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients' recovery time. [ABSTRACT FROM AUTHOR]

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID‐19). Totally, 75 COVID‐19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0–400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID‐19 patients relative to the single‐agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short‐term application. [ABSTRACT FROM AUTHOR]

The environmental risks resulting from the increasing antivirals in water are largely unknown, especially in eutrophic lakes, where the complex interactions between algae and drugs would alter hazards. Herein, the environmental risks of the antiviral drug arbidol towards the growth and metabolism of Microcystis aeruginosa were comprehensively investigated, as well as its biotransformation mechanism by algae. The results indicated that arbidol was toxic to Microcystis aeruginosa within 48 h, which decreased the cell density, chlorophyll-a, and ATP content. The activation of oxidative stress increased the levels of reactive oxygen species, which caused lipid peroxidation and membrane damage. Additionally, the synthesis and release of microcystins were promoted by arbidol. Fortunately, arbidol can be effectively removed by Microcystis aeruginosa mainly through biodegradation (50.5% at 48 h for 1.0 mg/L arbidol), whereas the roles of bioadsorption and bioaccumulation were limited. The biodegradation of arbidol was dominated by algal intracellular P450 enzymes via loss of thiophenol and oxidation, and a higher arbidol concentration facilitated the degradation rate. Interestingly, the toxicity of arbidol was reduced after algal biodegradation, and most of the degradation products exhibited lower toxicity than arbidol. This study revealed the environmental risks and transformation behavior of arbidol in algal bloom waters. [Display omitted] • The environmental risks of arbidol (ARB) in eutrophic lakes were firstly investigated. • ARB was hazardous to the growth and metabolism of M. aeruginosa within 48 h. • The synthesis and release of MCs by M. aeruginosa were promoted by ARB exposure. • ARB can be degraded by intracellular enzymes via loss of thiophenol and oxidation. • The toxicity of the ARB solution was decreased after M. aeruginosa biodegradation. [ABSTRACT FROM AUTHOR]

Chronic liver diseases (CLD) impact over 800 million people globally, causing about 2 million deaths annually. Arbidol (ARB), an indole-derivative used to treat influenza virus infection, was extensively used during COVID-19 pandemic in China. In recent years, studies have shown that ARB, compared to other antiviral drugs, exhibits greater liver-protective efficacy, indicating a potential hepatoprotective effect beyond its antiviral activity. However, the mechanism remains unclear. In this study, we investigated the impact of ARB on liver injury/fibrosis in bile duct ligated (BDL) mice and its effect on spontaneous and transforming growth factor β1 (TGF-β1)-induced activation of primary cultured hepatic stellate cells (HSCs). Oral administration of ARB significantly ameliorated BDL-induced liver injury/fibrosis as reflected by decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced collagen deposition, and diminished mRNA expression of fibrosis markers. ARB notably inhibited spontaneous and TGF-β1-induced activation of primary cultured HSCs. Moreover, ARB also drastically attenuated mRNA expression levels of platelet-derived growth factor receptor (Pdgfr), transforming growth factor-beta receptor (Tgfbr) 1, Tgfbr2, matrix metalloproteinase (Mmp)-2, and Mmp-9 in activated HSCs. We further demonstrate that ARB mitigated Smad2/3 phosphorylation in both TGF-β1 treated HSCs and BDL mice. These data together demonstrate that the therapeutic efficacy of ARB on liver fibrosis is independent of its antiviral activity and likely is achieved by blocking TGF-β1 signaling-mediated HSC activation. Arbidol hydrochloride (ARB) has been used to treat hepatitis caused by chronic hepatitis B virus (HBV), hepatitis C virus (HCV), and COVID-19. However, the mechanism of its hepatoprotective effect remains elusive. Here, we demonstrate that ARB alleviates liver fibrosis in a bile duct ligation mouse model suggesting its potential use in the treatment of liver fibrosis. ARB protection on liver injury and fibrosis is beyond its anti-viral activity, likely through regulation of TGF-β1 signaling pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

• The analysis distinguishes between "opened" and "closed" conformations based on the angle, revealing distinct alignment patterns of the phenyl ring around the indole moiety. • The study utilizes nuclear Overhauser effect spectroscopy to confirm the presence of distinct conformer groups and their internuclear distances in supercritical carbon dioxide. • The study concludes that the "closed" conformer group is the preferred conformation in supercritical carbon dioxide, aligning with previous findings. • The research highlights the potential of supercritical carbon dioxide as a promising medium for developing new forms of arbidol, shedding light on its conformational behavior. Arbidol is a pharmaceutical compound of significant importance due to its versatile applications in antiviral and Immunomodulatory therapies. The present study reports on the identification of multiple arbidol conformers in a supercritical carbon dioxide solution. The conformers were characterized based on various dihedral angles and the analysis of NOESY spectra. The study reveals distinct conformer groups, namely the "opened" and "closed" conformations, based on the angle τ 2 that governs the alignment of the phenyl ring around the indole moiety of the compound. The analysis of the chemical shifts in the 1H NMR spectra of ARB in different solvents (supercritical carbon dioxide, deuterochloroform, and hexadeutero-dimethyl sulfoxide) reveals variations in the proton signals, indicating changes in the conformation of arbidol molecules and the impact of ring currents from the phenyl fragment. The nuclear Overhauser effect spectroscopy analysis of arbidol in supercritical carbon dioxide confirms the presence of distinct conformer groups and their internuclear distances. The distances H22-H25/29 and H22-H10 are found to be indicative of the "closed" conformer group, with values consistent with previous studies. The proportions of "opened" and "closed" conformer groups in supercritical carbon dioxide are calculated using the experimental distances and compared with theoretical calculations. The preference of the conformer group in supercritical carbon dioxide is found to be the "closed" group, similar to previous studies on arbidol forms. Overall, this study provides insights into the conformational behavior of arbidol in supercritical carbon dioxide and highlights the potential of supercritical carbon dioxide as a promising medium for developing new arbidol forms. [ABSTRACT FROM AUTHOR]

Aim: To compare the safety and prophylactic efficacy of Cytovir-3 and Arbidol in an open-label randomized clinical trial in children at seasonal risk of infectious respiratory disease.Methods: This study was performed in the period preceding a seasonal outbreak of acute respiratory viral infections (ARVI) and influenza. The study enrolled apparently healthy children aged 6 to 18 years without contra-indications to either Cytovir-3 or Arbidol. Cytovir-3 was given as 1 capsule per day, each day in a fasted state for 12 days. Arbidol was taken as a 100 mg capsule twice a week for three weeks. Following dosing, subjects were followed-up for a further three weeks. Overall health and presence of symptoms of either ARVI or influenza were monitored daily in all subjects. The level of sIgA in saliva was baselined before treatment and measured at the end of the follow-up period.Results: Most subjects did not exhibit any change in overall health status during the dosing and follow-up periods. The first two cases of illness in subjects receiving Cytovir-3 were diagnosed at the end of the third week after completion of dosing. In those subjects receiving Arbidol the first cases of illness were reported at the end of the second week following the end of prophylactic dosing. All patients displayed a significant increase in sIgA level at the end of the dosing period, but this was more pronounced in the Cytovir-3 group. Conclusion: The results of this comparative randomized clinical trial confirmed the safety and tolerability of both medications, and that the prophylactic efficacy of Cytovir-3 is equal to that of Arbidol.

In spite of vaccination was recommended by the World Health Organization, the main strategy of influenza is antiviral drugs treatment, one of which is umifenovir. Aim. The aim of the study is to obtain additional data on safety and therapeutic efficacy of the antiviral drug Arbidol (umifenovir) in patients with a diagnosis of influenza and common cold. Materials and methods. Double-blind, randomized, placebo-controlled clinical study investigating efficacy and safety of Arbidol (umifenovir) in Treatment and Prophylaxis of Influenza and Common Cold (ARBITR) IV phase started in November 2011 and completed in April 2016 on the basis of 15 research centers in various regions of the Russian Federation. A total of 359 patients, aged 18 to 65 years with influenza or acute respiratory tract infection, of no more than 36 hours' duration were enrolled in the study. Patients were randomized into two groups: a group of patients (therapy group) treated by Arbidol (umifenovir) at a dosage of 800 mg/day (2 capsules) for 5 days (n=181), and a group of patients receiving placebo 4 times a day for 5 days (n=178). The primary outcome measures of the study were the duration of clinical illness among patients with common cold and influenza/ARVI, the duration and severity of the main symptoms. Number of clinical complications associated with influenza and common cold was assessed as a secondary outcome. Safety was assessed by analyzing number of adverse events that are probably or definitely related to Arbidol, assessing vital signs, examining the physical condition of patients and general clinical laboratory parameters. Results. In the group treated by umifenovir, the number of full recover patients on the 4th day from the disease onset were significantly differed from the number of such cases in the placebo group. The number of cases of complete recovery after 96 hours was 98 patients (54.1%) and 77 (43.3%), p

The magnitude of the risks in the face of the COVID-19 disease is increasing every day, and foreshadowing a catastrophe facing humanity. It is clear, the levels of health services in different countries around the world are very different, therefore there will be many health risks in countries that are suffering in terms of health services. The objective of this study was to compare different therapy for patients with severe coronaviruses diseases (COVID-19). Nowadays, different medicines have been used to reduce the severity of symptoms of this disease such as Ribavirin, Chloroquine, Arbidol, Lopinavir/Ritonavir, Favipiravir, Remdesivir, Azithromycin, and Sputnik V. These medications are used in every region of the world to make some progress in finding a solution to (COVID-19), including Kurdistan region which is in the north of Iraq. As is the case in most third world countries, the health service is not at the required level, and despite that, we were able to make a comprehensive list of medicines used in many countries of the world and here in Kurdistan, Iraq. In addition to this narrative and comparison of the best medication used to treat this pandemic, we also surveyed the opinions of over 100 people on the medicines discussed in this study throughout their treatment. The medicinal properties of medications used for COVID-19 and the results of their use on humans were studied in this review to promote appropriate medications for the treatment of coronavirus. [ABSTRACT FROM AUTHOR]

From the perspective of epidemiology, viral immunology and current clinical research, pulmonary fibrosis may become one of the complications of patients with Coronavirus Disease 2019 (COVID-19). Cytokine storm is a major cause of new coronavirus death. The purpose of this study was to explore the effects of antiviral drug arbidol on cytokine storm and pulmonary fibrosis. Here, we use a mouse model of bleomycin-induced pulmonary fibrosis and a mouse model of fecal dilution-induced sepsis to evaluate the effects of arbidol on pulmonary fibrosis and cytokine storm. The results showed that arbidol significantly reduced the area of pulmonary fibrosis and improved lung function (reduced inspiratory resistance, lung dynamic compliance and forced vital capacity increased). Treatment with arbidol promoted reduced sepsis severity 48 h after sepsis induction, based on weight, murine sepsis score and survival rate. Arbidol observably alleviates inflammatory infiltrates and injury in the lungs and liver. Finally, we also found that arbidol reduced serum levels of pro-inflammatory factors such as TNF-α and IL-6 induced by fecal dilution. In conclusion, our results indicate that arbidol can alleviate the severity of pulmonary fibrosis and sepsis, and provide some reference for the treatment of cytokine storm and sequelae of pulmonary fibrosis in patients with COVID-19.

Deep eutectic solvents are a new generation of green solvents composed of hydrogen bond acceptors and donors. However, when used as extractants in liquid–liquid separation, they are difficult to recycle and easy to lose. In order to solve these problems, herein, immobilized hydrogen bond acceptor adsorbent material was prepared for the separation and enrichment of antiviral drug arbidol from seven kinds of environmental water samples by in situ formation of hydrophobic deep eutectic solvents. The structure, morphology and thermal stability of the adsorbents were characterized, the separation and enrichment conditions for the targeted analyte were optimized, and the adsorption thermodynamics and kinetics were investigated. It was found that the adsorbent material could effectively enrich trace arbidol with the recovery more than 95% at the concentration above 7.5 ng/mL, and the enrichment factor was as high as 634.7. Coexisting substances, such as NaCl, KCl, CaCl2 and MgCl2, did not interfere with the adsorption of arbidol, even if their concentration was high, up to 1.0 mol/L, and the relative recovery for real samples was in the range from 92.5% to 100.3%. Furthermore, the immobilized hydrogen bond acceptor could be recycled and reused, and the recovery of arbidol was still above 95% after 12 adsorption–desorption cycles. The mechanism study demonstrates that the synergistic effect of hydrogen bonding and π-π stacking is the primary factor for the high adsorption efficiency.