biostudies-literatureParigger LÖsterreichische Forschungsförderungsgesellschaft1061142https://www.ebi.ac.uk/biostudies/studies/S-EPMC9794616biostudies-literatureUnknown9<h4>Introduction</h4>The current coronavirus pandemic is being combated worldwide by nontherapeutic measures and massive vaccination programs. Nevertheless, therapeutic options such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main-protease (M^pro) inhibitors are essential due to the ongoing evolution toward escape from natural or induced immunity. While antiviral strategies are vulnerable to the effects of viral mutation, the relatively conserved M^pro makes an attractive drug target: Nirmatrelvir, an antiviral targeting its active site, has been authorized for conditional or emergency use in several countries since December 2021, and a number of other inhibitors are under clinical evaluation. We analyzed recent SARS-CoV-2 genomic data, since early dFrontiers in medicineRecent changes in the mutational dynamics of the SARS-CoV-2 main protease substantiate the danger of emerging resistance to antiviral drugs.PMC979461641404876Parigger LGruber CCKrassnigg ASchopper TGruber KTappler KSingh AHetmann MSteinkellner GKochl KfalseRecent changes in the mutational dynamics of the SARS-CoV-2 main protease substantiate the danger of emerging resistance to antiviral drugs.<h4>Introduction</h4>The current coronavirus pandemic is being combated worldwide by nontherapeutic measures and massive vaccination programs. Nevertheless, therapeutic options such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main-protease (M^pro) inhibitors are essential due to the ongoing evolution toward escape from natural or induced immunity. While antiviral strategies are vulnerable to the effects of viral mutation, the relatively conserved M^pro makes an attractive drug target: Nirmatrelvir, an antiviral targeting its active site, has been authorized for conditional or emergency use in several countries since December 2021, and a number of other inhibitors are under clinical evaluation. We analyzed recent SARS-CoV-2 genomic data, since early d2022-01-01T00:00:00Z20222026-05-31T23:12:59.608Z2024-11-12T07:22:12.129ZS-EPMC97946163659097710.3389/fmed.2022.1061142