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Mapping Major Sars-Cov-2 Drug Targets And Assessment Of Druggability Using Computational Fragment Screening: Identification Of An Allosteric Small-Molecule Binding Site On The Nsp13 Helicase., Matthew R Freidel, Roger S Armen

College of Pharmacy Faculty Papers

The 2019 emergence of, SARS-CoV-2 has tragically taken an immense toll on human life and far reaching impacts on society. There is a need to identify effective antivirals with diverse mechanisms of action in order to accelerate preclinical development. This study focused on five of the most established drug target proteins for direct acting small molecule antivirals: Nsp5 Main Protease, Nsp12 RNA-dependent RNA polymerase, Nsp13 Helicase, Nsp16 2'-O methyltransferase and the S2 subunit of the Spike protein. A workflow of solvent mapping and free energy calculations was used to identify and characterize favorable small-molecule binding sites for an aromatic pharmacophore …