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

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.

Nirmatrelvir Plus Ritonavir: First Approval

“…Nirmatrelvir demonstrated antiviral activity against SARS-CoV-2 infection of differentiated normal human bronchial epithelial (dNHBE) cells treated with varying doses of nirmatrelvir for 3 days [half-maximal effective concentration (EC 50 ) and EC 90 values 61.8 nM and 181 nM] [ 6 , 10 , 16 ]. In accordance with the target protein of nirmatrelvir being highly conserved, the potency of nirmatrelvir against current variants of SARS-CoV-2 is similar to that against wild-type SARS-CoV-2 [ 22 , 23 ]. Nirmatrelvir had consistent cell culture antiviral activity (median EC 50 values ≤ 0.28 μM and < 3-fold relative to GHB-03021/2020) against isolates belonging to the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) SARS-CoV-2 variants of concern [ 22 ].…”

“…In accordance with the target protein of nirmatrelvir being highly conserved, the potency of nirmatrelvir against current variants of SARS-CoV-2 is similar to that against wild-type SARS-CoV-2 [ 22 , 23 ]. Nirmatrelvir had consistent cell culture antiviral activity (median EC 50 values ≤ 0.28 μM and < 3-fold relative to GHB-03021/2020) against isolates belonging to the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) SARS-CoV-2 variants of concern [ 22 ].…”

Antiviral activity of molnupiravir against COVID-19: a schematic review of evidences

“…Molnupiravir has also been shown to be effective against additional versions of SARS-CoV-2, including as the Omicron form, both alone and in combination with nirmatrelvir (Li et al 2022 ). Other variations such as alpha, beta, gamma, and delta were also shown to be molnupiravir-susceptible (Vangeel et al 2022 ).…”

Molnupiravir: First Approval

“…Molnupiravir inhibited SARS-CoV-2 in cell culture assays, with 50% effective concentrations (EC 50 ) ranging between 0.32 and 2.66 µM [7]. Molnupiravir has broad-spectrum in vitro activity against SARS-CoV-2 variants of concern such as B1.1.529 (omicron) [21][22][23][24][25][26], and B.1.1.7 (alpha), B.1351 (beta), P.1 (gamma) and B.1.617.2 (delta) [7]. The EC 50 values were 1.86-1.95 μM [21], and 1.59, 1.77, 1.32 and 1.68 μM [7], respectively.…”

“…Molnupiravir has broad-spectrum in vitro activity against SARS-CoV-2 variants of concern such as B1.1.529 (omicron) [21][22][23][24][25][26], and B.1.1.7 (alpha), B.1351 (beta), P.1 (gamma) and B.1.617.2 (delta) [7]. The EC 50 values were 1.86-1.95 μM [21], and 1.59, 1.77, 1.32 and 1.68 μM [7], respectively. In immunodeficient mice implanted with human lung tissue, therapeutic and prophylactic administration of molnupiravir inhibited SARS-CoV-2 replication in vivo [27].…”