Abstract 1579 Analogs of NIH Molecular Probe ML283 Identify a Possible Druggable Pocket on the SARS-CoV-2 nsp13 Helicase

RNA virus-encoded helicases are essential for viral replication yet with sufficiently similar structures that antivirals targeting one might work well for many other pathogens with pandemic potential. This study examines the effects of National Institutes of Health molecular probe ML283 and 53 related compounds on the SARS-CoV-2 nsp13 helicase. ML283 was synthesized as a potent, selective inhibitor of the helicase encoded by the hepatitis C virus. Unlike prior work with the HCV and Dengue virus helicase, there appears to be an apparent disconnect between the ability of the ML283 analogs to inhibit both unwinding and helicase-catalyzed ATP hydrolysis.