Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit

Abstract

The NIH Virtual SARS-CoV-2 Antiviral Summit, held on November 6, 2020, was organized to provide an overview on the status and challenges in developing antiviral therapeutics for COVID-19, including combinations of antivirals. Scientific experts from the public and private sectors convened virtually during a live videocast to discuss SARS-CoV-2 targets for drug discovery as well as the preclinical tools needed to develop and evaluate effective small molecule antivirals. The goals of the Summit were to review the current state of the science, identify unmet research needs, share insights and lessons learned from treating other infectious diseases, identify opportunities for public-private partnerships, and assist the research community in designing and developing antiviral therapeutics. This report includes an overview of therapeutic approaches, individual panel summaries, and a summary of the discussions and perspectives on the challenges ahead for antiviral development.

Molnupiravir: coding for catastrophe

“…Vaccine shortages, public hesitancy and the emergence of new virus variants have hindered public health efforts to prevent the spread of COVID-19. Furthermore, SARS-CoV-2 is likely to become endemic 1 , leading to the emergence of vaccine-resistant variants and reinforcing the need to develop antiviral therapeutic agents. Molnupiravir (MK-4482, EIDD-2801) is a candidate antiviral that inhibits viral propagation through lethal mutagenesis by introducing errors in the viral genome.…”

“…Similar to other nucleoside analogs, molnupiravir targets the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which mediates replication and transcription of the coronavirus genome. Viral RdRps are proven effective targets for inhibition, with several licensed nucleoside analogs that are used therapeutically 1,4 . Indeed, the only currently clinically approved antiviral used for the treatment of COVID-19 is remdesivir (Verklury), which targets the RdRp 5 .…”

Clinical drug therapies and biologicals currently used or in clinical trial to treat COVID-19

“…Apart from monoclonal antibody therapies, which can be administered in an out-patient setting, all other clinical trials were conducted on patients that had been admitted to the hospital. Moving forward, the NIH SARS-CoV-2 Antiviral Therapeutics Summit members outlined multiple principles that should go into future development of antivirals that could be taken at home [178] . Moreover, the drug should be potent against SARS-CoV-2, have bioavailability to the sites of infection, and have limited cytotoxicity.…”

SARS-CoV-2: Current trends in emerging variants, pathogenesis, immune responses, potential therapeutic, and vaccine development strategies

“…These inhibitory functions promote viral replication and lead to disease severity at the initial stages of infection. CoVs also mimic the capping machinery of target cells via nsp14 and nsp16 in order to avoid immune system recognition [138] . Nsp3 also produces two functional proteins, macrodomain-x, and PLpro, involved in the immune system avoidance process [45] , [139] , [140] .…”