Mutations E166V – L50F+E166V On SARS-CoV-2 Variants Weakens Nirmatrelvir 

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A new study by researchers from the Copenhagen University Hospital-Denmark, the Department of Immunology and Microbiology at the University of Copenhagen-Denmark and the Technical University of Denmark has found that the mutations E166V and L50F+E166V that are found on various emerging SARS-CoV-2 variants, weakens nirmatrelvir-Mpro binding.

Nirmatrelvir, an oral protease inhibitor is an important component of the drug Paxlovid, of which those controlling the COVID-19 narratives are currently trying to promote extensively despite emerging data showing that it is yet another literally ineffective overpriced drug with long term toxic effects, similar the U.S. NIH and U.S. FDA promoted remdesivir and molnupiravir.

The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2022.06.06.494921v1

The oral protease inhibitor nirmatrelvir is expected to play a pivotal role for prevention of severe cases of coronavirus disease 2019 (COVID-19).

To facilitate monitoring of potentially emerging resistance, we studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape from nirmatrelvir. Resistant variants selected in cell culture harbored different combinations of substitutions in the SARS-CoV-2 main protease (Mpro).

Reverse genetic studies in a homologous infectious cell culture system revealed up to 80-fold resistance conferred by the combination of substitutions L50F and E166V. Resistant variants had high fitness increasing the likelihood of occurrence and spread of resistance. Molecular dynamics simulations revealed that E166V and L50F+E166V weakened nirmatrelvir-Mpro binding.

The SARS-CoV-2 polymerase inhibitor remdesivir retained activity against nirmatrelvir resistant variants and combination of remdesivir and nirmatrelvir enhanced treatment efficacy compared to individual compounds. These findings have implications for monitoring and ensuring treatment programs with high efficacy against SARS-CoV-2 and potentially emerging coronaviruses.

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