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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]

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 The Author(s). Published by Elsevier B.V. All rights reserved.)

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]

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

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]

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.

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]

• 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

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.

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. [ABSTRACT FROM AUTHOR]

ObjectiveSince the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan City, China, coronavirus disease 2019 (COVID-19) has become a global pandemic. However, no special therapeutic drugs have been identified for COVID-19. The aim of this study was to search for drugs to effectively treat COVID-19.Materials and MethodsWe conducted a retrospective cohort study with a total of 162 adult inpatients (≥18 years old) from Ruijin Hospital (Shanghai, China) and Tongji Hospital (Wuhan, China) between January 27, 2020, and March 10, 2020. The enrolled COVID-19 patients were first divided into the Lianhuaqingwen (LHQW) monotherapy group and the LHQW + Arbidol combination therapy group. Then, these two groups were further classified into moderate and severe groups according to the clinical classification of COVID-19.ResultsThe early combined usage of LHQW and Arbidol can significantly accelerate the recovery of patients with moderate COVID-19 by reducing the time to conversion to nucleic acid negativity, the time to chest CT improvement, and the length of hospital stay. However, no benefit was observed in severe COVID-19 patients treated with the combination of LHQW + Arbidol. In this study, both Arbidol and LHQW were well tolerated without serious drug-associated adverse events.ConclusionThe early combined usage of LHQW and Arbidol may accelerate recovery and improve the prognosis of patients with moderate COVID-19.

Background: Frontline health professionals are a COVID-19-susceptible population during the outbreak of COVID-19, but prophylactic drugs against SARS-CoV-2 infection are to be explored.Method: Frontline health professionals diagnosed with COVID-19 before February 9, 2020 in Tongji Hospital, Wuhan, China and the same amount of controls in the uninfected group were included in this study. Clinical and laboratory data were collected with standardized forms.Results: A total of 164 subjects were included in this study, 82 cases in the infected group and 82 controls in the uninfected group, with a median age of 37 years, including 63 males and 101 females. Nineteen (23.2%) patients in the infected group were administered oral arbidol, and 48 (58.5%) in the uninfected group (OR = 0.214, 95% CI 0.109–0.420). The cumulative uninfected rate of health professionals in the arbidol group was significantly higher than that of individuals in the non-arbidol group (log-rank test, χ2 = 98.74; P < 0.001). Forty-eight patients (58.5%) in the infection group were hospitalized, with a median age of 39 (31–49) years, of whom 7 (14.6%) were prophylactically administered arbidol. Thirty-four patients (41.5%) with mild symptoms were treated outside the hospital, among which the median age was 34 (30–39) years, and twelve patients (35.3%) took prophylactic oral arbidol. The hospitalization rate was significantly associated with age (P = 0.024) and oral arbidol administration (OR = 0.313, 95% CI 0.108–0.909). In the age-matched case-control study, the hospitalization rate was not significantly associated with arbidol administration (P = 0.091).Conclusion: Prophylactic oral arbidol was associated with a lower incidence of SARS-CoV-2 infection but not hospitalization rate in health professionals, providing a basis for the selection of prophylactic drugs for high-risk populations.

In this work, we evaluated the antiviral activity of Arbidol (Umifenovir) against SARS-CoV-2 using a pseudoviral system with the glycoprotein S of the SARS-CoV-2 virus on its surface. In order to search for binding sites to protein S of the virus, we described alternative binding sites of Arbidol in RBD and in the ACE-2-RBD complex. As a result of our molecular dynamics simulations combined with molecular docking data, we note the following fact: wherever the molecules of Arbidol bind, the interaction of the latter affects the structural flexibility of the protein. This interaction may result both in a change in the shape of the domain–enzyme binding interface and simply in a change in the structural flexibility of the domain, which can subsequently affect its affinity to the enzyme. In addition, we examined the possibility of Arbidol binding in the stem part of the surface protein. The possibility of Arbidol binding in different parts of the protein is not excluded. This may explain the antiviral activity of Arbidol. Our results could be useful for researchers searching for effective SARS-CoV-2 virus inhibitors targeting the viral entry stage.

Aim. To assess the efficacy and safety of Arbidol in the influenza and ARVI preventing in patients with asthma and chronic obstructive pulmonary disease (COPD). Materials and methods. This study was an open label and prospective during epidemic period of 2016-2017 years. 100 outpatients aged 18 to 80 years with verified asthma and/or COPD, were enrolled to therapy group, and received oral umifenovir 200 mg once daily for 14 days and then 200 mg twice a week for 3 weeks.The medical records data for the same epidemic period of 2016-2017 seasons of the same patients during witch they received no prophylaxis was taken as a control. The data analysis was made by applying parametric and nonparametric statistical methods. Results and discussion. Seasonal and post-exposure prophylaxis using umifenovir was associated with 2.6-times reduction in influenza and ARVI morbidity compared to control. In diseased patients (ARVI) of the therapy group the number of patients with mild illness prevailed (62.2%) and was significantly differed from control (37.1%). Severity of catarrhal symptoms and intoxication, was reduced with umifenovir prophylaxis course and were mild in 67.6% and 67.6% respectively of therapy group compared with 43.3% and 46.4% of control. Influenza and ARVI complications were only detected in control group (4 cases). The percentage of patients with incidents of underlying disease exacerbation was 42% in therapy group and 93% in control group. Also, exacerbation in the therapy group were mild in 59.5% and 34.4% in control group, while moderate exacerbation prevailed in control group and was in 59.1% of cases with was significantly higher then in therapy group (39.3%). Results in more frequent use of adjuvant in the control group compared with the therapy group (81.7% and 59.5% respectively). Patients of control group had a higher risk of hospitalizations due to underlying disease aggravation (11.8%), compared with therapy group (9.5%) but these differences were not significant. Coclusion. Seasonal and post-exposure prophylaxis with Arbidol reduce influenza and ARVI morbidity in patients with asthma and COPD during epidemic period, frequency and severity of chronic obstructive pulmonary disease aggravations resulting in decrease in the number of hospitalizations. Also, prophylaxis with Arbidol reduced the severity of catarrhal symptoms and intoxication.

BACKGROUND: COVID-19 is not fully known and causes severe inflammation and cytokine storm. It has many symptoms, such as: fever, sore throat, headache, dyspnoea, and diarrhoea. Arbidol was used in the treatment of COVID19, which was the most critical health problem in the world. However, the desired recovery was not achieved with Arbidol. Many countries still use this drug in the treatment of COVID19. AIM: We aimed to determine whether Arbidol, the hemagglutinin esterase inhibitor used in the treatment of COVID-19, was effective against SARS Cov-2 in silico. RESULTS AND CONCLUSION: The similarity between hemagglutinin and spike proteins were reported due to the fact that inhibition properties of Arbidol and its 39 analogues were examined in detail against hemagglutinin esterase and spike glycoproteins. CID 1070884 and CID 1207786 were found to be more active against hemagglutinin esterase than in Arbidol, while these compounds were inactive against spike glycoproteins. The interaction mechanism was clarified between arbidol and spike proteins. Phenylalanine, tyrosine, glycine, lysine, and aspartic acid were found to be the headliner amino acids in the interactions between Arbidol and binding domains of spike glycoproteins in the SARS-CoV2. [ABSTRACT FROM AUTHOR]

Objective: Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan City, China, coronavirus disease 2019 (COVID-19) has become a global pandemic. However, no special therapeutic drugs have been identified for COVID-19. The aim of this study was to search for drugs to effectively treat COVID-19. Materials and Methods: We conducted a retrospective cohort study with a total of 162 adult inpatients (≥18 years old) from Ruijin Hospital (Shanghai, China) and Tongji Hospital (Wuhan, China) between January 27, 2020, and March 10, 2020. The enrolled COVID-19 patients were first divided into the Lianhuaqingwen (LHQW) monotherapy group and the LHQW + Arbidol combination therapy group. Then, these two groups were further classified into moderate and severe groups according to the clinical classification of COVID-19. Results: The early combined usage of LHQW and Arbidol can significantly accelerate the recovery of patients with moderate COVID-19 by reducing the time to conversion to nucleic acid negativity, the time to chest CT improvement, and the length of hospital stay. However, no benefit was observed in severe COVID-19 patients treated with the combination of LHQW + Arbidol. In this study, both Arbidol and LHQW were well tolerated without serious drug-associated adverse events. Conclusion: The early combined usage of LHQW and Arbidol may accelerate recovery and improve the prognosis of patients with moderate COVID-19. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Umifenovir (Arbidol®) is an antiviral drug being used to treat influenza in Russia and China. This study aimed to investigate the effectiveness and safety of umifenovir for COVID-19. A retrospective study was performed in a non-intensive care unit (ICU) ward in Jinyintan Hospital from 2 February 2020 to 20 March 2020. COVID-19 was confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) assay of pharyngeal swab specimens. The confirmed patients were divided into the umifenovir group and the control group according to the use of umifenovir. The main outcomes were the rate of negative pharyngeal swab tests for SARS-CoV-2 within 1 week after admission and the time for the virus to turn negative. The negativity time of SARS-CoV-2 was defined as the first day of a negative test if the nucleic acid of SARS-CoV-2 was negative for two consecutive tests. A total of 81 COVID-19 patients were included, with 45 in the umifenovir group and 36 in the control group. Baseline clinical and laboratory characteristics were comparable between the two groups. Thirty-three out of 45 (73%) patients in the umifenovir group tested negative for SARS-CoV-2 within 7 days after admission, the number was 28/36 (78%) in the control group (p 0.19). The median time from onset of symptoms to SARS-CoV-2 turning negative was 18 days (interquartile range (IQR) 12–21) in the umifenovir group and 16 days (IQR 11–21) in the control group (p 0.42). Patients in the umifenovir group had a longer hospital stay than patients in the control group (13 days (IQR 9–17) vs 11 days (IQR 9–14), p 0.04). No deaths or severe adverse reactions were found in both groups. Umifenovir might not improve the prognosis or accelerate SARS-CoV-2 clearance in non-ICU patients. A randomized control clinical trial is needed to assess the efficacy of umifenovir. [ABSTRACT FROM AUTHOR]

The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10–14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2 b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment. [ABSTRACT FROM AUTHOR]

Insights into COVID-19 antivirals' environmental fate and ecological risk are urgently required due to their increasing concentrations in aquatic environments, which have rarely been studied. Herein, we first investigated the photochemical transformation and the resulting alterations in toxicity of arbidol, an antiviral drug with relatively higher toxicity. The photolysis of arbidol was rapid with a rate constant of 0.106 min−1 due to its superior ultraviolet light absorption, in which the direct photolysis was predominated with a contribution of 91.5%. Despite its substantial photolysis, only 14.45% of arbidol was mineralized after 100 min, implying that arbidol and its products might have a long-term impact on aquatic environment. It was inferred that arbidol was photolyzed mainly via the loss of thiophenol, bromine, and alkylamine, based on twelve photolytic products identified. Notably, the experimental results demonstrated that the photolysis process increased the acute toxicity of arbidol, and the toxicity prediction indicated that the ecotoxicity of two photolytic products was very high with LC 50 values below 0.1 mg/L. Due to the co-effect of multiple constituents, the photolytic rate observed in wastewater treatment plant effluent and in river water was comparable to that in ultra-pure water, while it was slightly enhanced in lake water. The presence of dissolved organic matter suppressed arbidol photolysis, while NO 3 − exhibited a promotion effect. These results would be of great significance to assess the fate and risk of COVID-19 antivirals in natural aquatic environments. [Display omitted] • Sunlight-induced transformation and toxicity of arbidol (ARB) were first studied. • ARB underwent rapid photolysis upon light and direct photolysis was dominated. • Photolysis of ARB was suppressed by the presence of DOM and promoted by NO 3 −. • ARB was photolyzed mainly via the loss of thiophenol, bromine, and alkylamine. • Increased toxicity was induced by the photo-transformation of ARB. [ABSTRACT FROM AUTHOR]

Influenza is an acute respiratory disease that harms human health and leads to huge economic losses. The fight against this disease is included in the priorities of healthcare in many countries and has important medical and social importance [1, 2]. In addition to vaccination as the main strategy in the fight against flu, the World Health Organization recommends the use of antiviral drugs. The development of such drugs began in the 60s of the last century, when the scientists became to understand the subtle processes of viral replication and the ability to suppress its individual stages, without exerting a significant effect on the cells metabolic processes.

Aim. To assess correlation of cytokines levels and therapy regimes a relationship of the time course of changes in the cytokines IFN-γ, IFN-α, IL-18, and TNF-α to the treatment option for influenza A (H1N1) pdm09 with umifenovir (Arbidol) 800 mg/day for 5 days (n=50); oseltamivir (Tamiflu) 150 mg/day for 5 days (n=50); umifenovir (Arbidol) 800 mg/day for 5 days in combination with Kagocel 72 mg/day for 2 days.; 36 mg/day for 2 days (n=50); oseltamivir ((Tamiflu) (150 mg/day for 5 days) in combination with Kagocel 72 mg/day for 2 days; 36 mg/day for 2 days (n=50). A comparison group consisted of 30 healthy volunteers. Material and methods. The state of immunologic reactivity was assessed twice: at admission of the patients to an infectious disease clinic (at 1—3 disease days) and in the early convalescent period (at 7—8 disease days): venous blood samples were collected to determine the concentrations of IFN-γ, IFN-α, IL-18, and TNF-α by a solid-phase enzyme immunoassay. Results. All the patients in the acute phase of influenza A showed a statistically significant increase in the levels of IFN-γ, IFN-α, and IL-18 as compared with the control group. The groups receiving monotherapy in the early convalescent period had a decrease in the IFN-γ, IFN-α, and IL-18 concentrations that could be compensated by the combined use of the immunomodulator Kagocel. No statistically significant changes in the levels of TNF-α were found in the patients of all the groups, but the groups receiving monotherapy exhibited its lower concentrations in the convalescence period. Conclusion. The combination of etiotropic antiviral drugs with Kagocel enhances the efficiency of antiviral therapy. Monitoring of antiviral cytokines during the treatment of influenza A is a convenient tool to verify the efficiency of antiviral therapy and needs to be more widely introduced into medical practice.

Aim. To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). Materials and methods. The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. Results. The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. Conclusion. The FRs for influenza and ARVI complications are patient’s age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.

Thearticle presents the results of years of studies (including biochemical and immunological) of the effectiveness of application and prophylaxis (in relation to nosocomial infections) and the safety of antiviral chemical preparation Arbidol in 694 children with influenza and influenza-like illness, including the coronavirus infection (43 children) and combined lesions of respiratory tract (150), indicating the possible inclusion of the drug in the complex therapy for children with the listed diseases, regardless of the severity and nature of their course. The studies were conducted according to the regulated standard of test conditions and randomized clinical trials.

The article presents the results of the study of clinical and epidemiological data from 2044 children aged under 18 years who were hospitalized with influenza and other ARVI in the epidemic season 2010/11. The effectiveness of conducted antiviral therapy was also evaluated. The most frequently prescribed antiviral drug at prehospital and hospital stages was Arbidol. It is shown that early appointment of Arbidol significantly reduced the duration of the main symptoms of influenza and acute respiratory viral infections, and the risk of complications.