Discovery (Lead Identification)
Despite several partially effective prophylactic vaccines for SARS-CoV-2 exist, patients worldwide still succumb to COVID-19. New therapeutics to treat this disease are still needed. Upon host invasion, a critical step in the pathogenesis of COVID-19 is intracellular replication of SARS-CoV-2 before viral particles invade nearby healthy cells. This triggers an extreme inflammatory response that may lead to acute respiratory distress syndrome (ARDS) or transmission to another host. Therefore, therapeutics that can successfully curb the replication of SARS-CoV-2 are imperative.
Within host cells, the replication of SARS-CoV-2’s genome is catalyzed by RNA-dependent RNA Polymerase (RdRP). NIH investigators discovered that the nitroxide antioxidant, TEMPOL, interferes with RdRP’s assembly and activity, leading to reduced viral replication in vitro. This discovery suggests that TEMPOL could serve as an antiviral to treat patients with active SARS-CoV-2 infection.