In vitro effects of several antivirals on various SARS-CoV-2 mutants of concern

Independent studies show that current and future antiviral treatments, including remdecibir and oral neo-coronavirus disease 2019 (COVID-19) oral antiviral treatment, include Lagebrio (molnupiravir) Paxlovid (nilmatrelvir) with severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2).

study: Remdesivir, molnupiravir, and nilmatrelvir continue to be effective against SARS-CoV-2 omicrons and other variant of concern... Image Credits: Naeblys / Shutterstock

In late December 2021, the US Food and Drug Administration granted Emergency Use Authorization for Paxrovid and Lagebrio for mild to moderate COVID-19 infections in adults. They also approved Paxlovid for children over the age of 12 who show a significant risk of life-threatening illness and hospitalization.

Research published in bioRxiv* Awaiting preprint server and peer review, it was found that the treatment retained antiviral activity across several variant of concern variants, including Omicron.

Details of the study

Researchers exposed VeroE6-GFP cells to several antiviral COVID-19 treatments and then infected them with virus isolates from five of concern SARS-CoV-2 variants. The SARS-CoV-2 ancestral strain grew from the first Belgian patient sample. Researchers counted the number of fluorescent pixels from the GFP signal, as determined by image processing four days after infection.They measured the concentration of each drug at 50% Effectiveness For each variant.

The antiviral treatments studied were remdesivir, an oral analog of remdesivir GS-441524, the RNA polymerase inhibitors EIDD-1931 and Lagevrio, and the protease inhibitor Paxlovid.

Paxrovid, one of the first COVID-19 treatments in the form of tablets, works differently than the COVID-19 vaccine. This is because it targets the major proteases, not the COVID-19 vaccine. Spike proteinWhere most mutations from the variant of concern are present. The main protease is a cysteine ​​protease that cleaves the two polyproteins of SARS-CoV-2 at various locations. Doing so produces a large number of nonstructural proteins that are essential for viral replication. Paxlovid is co-prescribed with low doses of ritonavir to protect against severe COVID-19 illness and hospitalization if taken within the first few days of symptoms.

As a protease inhibitor, Paxrovid prevents the virus from replicating inside cells, reducing the possibility of the virus spreading throughout the body and causing serious illness.

Molnupiravir and EIDD-1931 were originally developed to prevent viral replication of other RNA viruses, including influenza. Recent clinical trial data from molnupirvair have shown that the drug promotes SARS-CoV-2 RNA clearance and shortens virus removal time.

result

All antiviral COVID-19 treatments showed similar antiviral activity against currently of concern mutant strains (alpha, beta, gamma, delta, omicron). Researchers suggest that this is likely due to the low number of mutant proteins in the antiviral target proteins compared to other SARS-CoV-2 regions.

RNA polymerase had two amino acid changes (P313L for all variants of concern and G661S for Delta) compared to the original SARS-CoV-2 strain. For the SARS-CoV-2 protease, there were three amino acid mutations, including alpha K90R, omicron P132H, and delta V296I. However, neither RNA polymerase nor SARS-CoV-2 protease mutations were present in the active site, and there was no difference in susceptibility.

Given the consistent antiviral activity across the mutants, the results strongly suggest that current COVID-19 treatment remains effective against future SARS-CoV-2 mutants. Having a wide range of antivirals beyond SARS-CoV-2 may help mitigate the effects of future viral outbreaks.

“Therefore, it is important to continue both vaccine development and antiviral research, both of which are essential armor and complement each other in current pandemic control strategies,” the research team concludes. I did.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.