Fig. 4.
Heat maps of the nirmatrelvir-bound Mpro mutations with their frequencies of occurrence retrieved from GISAID-enabled CoV-GLUE-Viz databases. Mutations at the nirmatrelvir-binding site of Mpro obtained from the GISAID-enabled CoV-GLUE-Viz databases are shown. Frequencies of the mutations in SARS-CoV-2 sequences from the COVID-19 pandemic ranged from lower to higher numbers and from blue to orange colors, respectively. The designed mutants that potentially developed resistance and adaptation towards nirmatrelvir are denoted as 'N' in red. It was found that out of 199 mutations, 78 mutations were predicted as positively selected and resistant in the design computations, therefore attaining ∼40% correlation, already exist in the SARS-CoV-2 sequences and are currently circulating. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)