molnupiravir and Coronavirus-Infections

On March 11, 2020, the World Health Organization (WHO) declared the outbreak of coronavirus disease (COVID-19) a pandemic. Since then, thousands of people have suffered and died, making the need for a treatment of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) more crucial than ever.. The authors carried out a search in PubMed, ClinicalTrials.gov and New England Journal of Medicine (NEJM) for COVID-19 to provide information on the most promising treatments against SARS-CoV-2.. Possible COVID-19 agents with promising efficacy and favorable safety profile were identified. The results support the combination of copper, N-acetylcysteine (NAC), colchicine and nitric oxide (NO) with candidate antiviral agents, remdesivir or EIDD-2801, as a treatment for patients positive for SARS-CoV-2.. The authors propose to study the effects of the combination of copper, NAC, colchicine, NO and currently used experimental antiviral agents, remdesivir or EIDD-2801, as a potential treatment scheme for SARS-COV-2.

Topics: Acetylcysteine; Adenosine Monophosphate; Adjuvants, Immunologic; Alanine; Anti-Inflammatory Agents; Antiviral Agents; Autophagy; Betacoronavirus; Colchicine; Copper; Coronavirus Infections; COVID-19; Cytidine; Drug Synergism; Drug Therapy, Combination; Humans; Hydroxylamines; Inflammation; Nitric Oxide; Pandemics; Pneumonia, Viral; Prodrugs; Ribonucleosides; SARS-CoV-2; Virus Internalization; Virus Replication

The coronavirus disease 2019 (COVID-19) that is wreaking havoc on worldwide public health and economies has heightened awareness about the lack of effective antiviral treatments for human coronaviruses (CoVs). Many current antivirals, notably nucleoside analogs (NAs), exert their effect by incorporation into viral genomes and subsequent disruption of viral replication and fidelity. The development of anti-CoV drugs has long been hindered by the capacity of CoVs to proofread and remove mismatched nucleotides during genome replication and transcription. Here, we review the molecular basis of the CoV proofreading complex and evaluate its potential as a drug target. We also consider existing nucleoside analogs and novel genomic techniques as potential anti-CoV therapeutics that could be used individually or in combination to target the proofreading mechanism.

Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytidine; Genome, Viral; Humans; Hydroxylamines; Molecular Targeted Therapy; Mutation; Pandemics; Pneumonia, Viral; Pyrazines; Ribonucleosides; RNA, Viral; SARS-CoV-2; Severity of Illness Index; Transcription, Genetic; Viral Nonstructural Proteins; Virus Replication

Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain viral RNA replication. Our study provided evidence for the dose-dependent inhibition of PEDV replication by molnupiravir in Vero cells. Molnupiravir also exhibited a strong inhibitory effect on viral RNA and protein production. Our results demonstrated that molnupiravir inhibits PEDV RNA-dependent RNA polymerase (RdRp) activity and induces a high frequency of mutations in the PEDV genome. Further studies revealed that molnupiravir can reverse changes in the transcriptome caused by viral infection. In conclusion, our results indicated that molnupiravir has the potential to be an effective treatment for PEDV infection.

Topics: Animals; Chlorocebus aethiops; Coronavirus; Coronavirus Infections; Hydroxylamines; Porcine epidemic diarrhea virus; Swine; Swine Diseases; Vero Cells

Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, β-D-N

Topics: Antiviral Agents; Common Cold; Coronavirus 229E, Human; Coronavirus Infections; Coronavirus NL63, Human; Coronavirus OC43, Human; Cytidine; Humans; Hydroxylamines; Molecular Docking Simulation; Protein Binding; Pyrrolidines; RNA-Dependent RNA Polymerase; Seasons; Sulfonic Acids; Virus Replication

Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; Birds; Clinical Trials as Topic; Coronavirus; Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytidine; Drug Development; Drug Industry; Europe; Humans; Hydroxylamines; Indoles; Influenza, Human; Leucine; Orthomyxoviridae; Pandemics; Pyrrolidinones; Severe Acute Respiratory Syndrome; Strategic Stockpile; United States

Topics: Adenosine Monophosphate; Alanine; Animals; Antibiotic Prophylaxis; Antiviral Agents; Betacoronavirus; Cell Line; Coronavirus Infections; COVID-19; Cytidine; Disease Models, Animal; Drug Resistance, Viral; Humans; Hydroxylamines; Lung; Mice; Mice, Inbred C57BL; Middle East Respiratory Syndrome Coronavirus; Models, Molecular; Mutation; Pandemics; Pneumonia, Viral; Primary Cell Culture; Random Allocation; Respiratory System; Ribonucleosides; RNA-Dependent RNA Polymerase; RNA, Viral; SARS-CoV-2; Virus Replication

Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Cytidine; Humans; Hydroxylamines; Pandemics; Pneumonia, Viral; Ribonucleosides; RNA-Dependent RNA Polymerase; SARS-CoV-2; Transcription, Genetic