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The coronavirus pandemic is combated worldwide by non-therapeutic measures and massive vaccination programs. Nevertheless, therapeutic options such as severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) main-protease (Mpro) inhibitors are essential due to the ongoing evolution toward escape from natural or induced immunity. The study analyzed recent SARS-CoV-2 genomic data since early detection of potential resistances supports a timely counteraction in drug development and deployment and discovered accelerated mutational dynamics of Mpro since early December 2021. The increased mutational variability in close proximity to an antiviral-drug binding site, as described herein, may suggest the onset of the development of antiviral resistance.
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