Anti-SARS-CoV-2 agent prodrug-1

Anti-SARS-CoV-2 agent prodrug-1 (compound 5b) (serial dilution; 24 h pretreatment, 4 days of antiviral incubation, 5 days of cytotoxicity incubation) potently inhibits SARS-CoV-2 in VeroE6-eGFP cells, with an EC₅₀ of 3.22 μM, extremely low cytotoxicity (CC₅₀ > 100 μM), and a selectivity index > 31.1^[1].
Anti-SARS-CoV-2 agent prodrug-1 is rapidly converted by esterases into compound 4, an intermediate with greater plasma metabolic stability; compound 4 can bypass the rate-limiting nucleoside monophosphorylation step via its ProTide moiety, and is rapidly activated enzymatically to release nucleoside monophosphate, exerting broad-spectrum antiviral activity^[1].
Anti-SARS-CoV-2 agent prodrug-1 (2.00 μM; 120 min) exhibits extremely low apparent intact permeability across Caco-2 cell monolayers, which may result from rapid intracellular hydrolysis and retention of polar metabolites after its cellular uptake^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.