A study 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 five mutated variants including Omicron. VeroE6-GFP cells were pre-treated with serial dilutions of the compounds before infection and the GFP signal was determined by high-content imaging on day 4 post-infection. 

All molecules showed equipotent antiviral activity against the ancestral virus and the Variants of Concerns (VOCs) like Alpha, Beta, Gamma, Delta and Omicron. These findings suggest that the target proteins of these antivirals (respectively the viral RNA dependent RNA polymerase and the viral main protease Mpro) are highly conserved.

In vitro results prove that GS-441524, remdesivir, EIDD-1931, molnupiravir and nirmatrelvir have activity against all current VOCs including Omicron. The maximal change of the median EC50s over the different VOC is for each compound was found to be < 3x (1.8x for GS-441524, 1.6x for remdesivir, 2.5x for the series EIDD-1931 and molnupiravir and 2.5x for nirmatrelvir), which are within the normal range of measurement error. 

Following are the highlights of the study-

• The omicron SARS-CoV-2 variant is found to be susceptible for GS-441524, Remdesivir, EIDD-1931, Molnupiravir and Nirmatrelvir.
• The target genes of these antivirals remain highly conserved between SARS-CoV-2 variants.
• The alpha, beta, gamma and delta variants also remain susceptible to these antivirals.

Source- Antiviral Research,2022;198. https://doi.org/10.1016/j.antiviral.2022.105252.