Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern

Laura Vangeel,Winston Chiu,Steven De Jonghe,Piet Maes,Bram Slechten,Joren Raymenants,Emmanuel André,Pieter Leyssen,Johan Neyts,Dirk Jochmans

doi:10.1016/j.antiviral.2022.105252

Abstract

We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against the ancestral SARS-CoV2 strain and the five variants of concern including Omicron. VeroE6-GFP cells were pre-treated overnight with serial dilutions of the compounds before infection. The GFP signal was determined by high-content imaging on day 4 post-infection. All molecules have equipotent antiviral activity against the ancestral virus and the VOCs Alpha, Beta, Gamma, Delta and Omicron. These findings are in line with the observation that the target proteins of these antivirals (respectively the viral RNA dependent RNA polymerase and the viral main protease Mpro) are highly conserved.

Highlights

We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against the ancestral SARS-CoV2 strain and the five variants of concern including Omicron
Several direct-acting antivirals against SARS-CoV-2 have been approved or are advancing in clinical development. They can be divided in two classes, monoclonal antibodies directed against the Spike protein and small molecules interfering with the viral replication ma chinery. mAbs are administered intravenously but studies are underway to explore intramuscular or subcutaneous administration which would overcome the requirement of a hospital setting for dosing. (Kumar et al, 2021)
The U.S FDA issued an emergency use authorization (EUA) in infected adults who are at high risk for progression to severe COVID-19, and for whom alternative COVID-19 treatment options are not accessible or clinically appropriate

Summary

Introduction

We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against the ancestral SARS-CoV2 strain and the five variants of concern including Omicron. One and a half year after the start of the global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), multiple variants have emerged. Several direct-acting antivirals against SARS-CoV-2 have been approved or are advancing in clinical development.

Results

Conclusion