Large scale analysis of the SARS-CoV-2 main protease reveals marginal presence of nirmatrelvir-resistant SARS-CoV-2 Omicron mutants in Ontario, Canada, December 2021-September 2023

In response to the COVID-19 pandemic, a new oral antiviral called nirmatrelvir-ritonavir (Paxlovid ) was authorized for use in Canada in January 2022. studies have reported mutations in M protein that may be associated with the development of nirmatrelvir resistance. To survey the prevalence, relevance and temporal patterns of M mutations among SARS-CoV-2 Omicron lineages in Ontario, Canada. A total of 93,082 M gene sequences from December 2021 to September 2023 were analyzed. Reported M mutations were screened against our database using in-house data science pipelines to determine the nirmatrelvir resistance. Negative binomial regression was conducted to analyze the temporal trends in M mutation counts over the study time period. A declining trend was observed in non-synonymous mutations of M sequences, showing a 7.9% reduction (95% CI: 6.5%-‬9.4%;