High-throughput rational design of the remdesivir binding site in the RdRp of SARS-CoV-2: implications for potential resistance

Summary The use of remdesivir to treat COVID-19 will likely continue before clinical trials are completed. Due the lengthening pandemic and evolving nature virus, predicting potential residues prone mutation is crucial for management resistance. Using a rational ligand-based interface design complemented with mutational mapping, we generated total 100,000 mutations provided insight into functional outcomes in remdesivir-binding site nsp12 subunit RdRp. After designing 46 nsp12, designs retained 97%–98% sequence identity, suggesting that very few required SARS-CoV-2 attain Several mutants displayed decreased binding affinity remdesivir, drug These hotspot had higher probability undergoing selective thus conferring Identifying improves our understanding resistance pathogenesis.