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Bemnifosbuvir + probenecid is an investigational combination therapy primarily studied for the treatment of COVID-19. Bemnifosbuvir (AT-527) is an oral, non-guanosine nucleotide analog prodrug that targets the viral RNA-dependent RNA polymerase (RdRp). Uniquely, it inhibits both the RdRp catalytic site and the nidovirus RNA-dependent RNA polymerase-associated nucleotidyltransferase (NiRAN) domain, which is involved in viral capping and is highly conserved across coronaviruses. Probenecid, a uricosuric agent and potent inhibitor of organic anion transporters (OAT1 and OAT3), is co-administered to enhance the pharmacokinetic profile of bemnifosbuvir. By inhibiting the renal secretion and potentially the cellular efflux of bemnifosbuvir's active metabolites, probenecid aims to increase systemic exposure and maintain therapeutic concentrations of the antiviral agent.
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