Olgotrelvir

Olgotrelvir (STI-1558) is an experimental antiviral medication being studied as a potential treatment for COVID-19. It is believed to work by inhibiting the SARS-CoV-2 main protease (Mpro), a key enzyme that SARS-CoV-2 needs to replicate,   and by blocking viral entry.

Mechanism of action
Olgotrelvir is a prodrug that first converts to its active form, AC1115. AC1115 is believed to work by inhibiting the SARS-CoV-2 main protease (also known as 3C-like protease). This protein is a crucial enzyme responsible for cleaving viral polyproteins into functional subunits essential for viral replication. By binding to the active site of the protease, the drug prevents this cleavage process, effectively halting viral assembly and impeding the virus's ability to produce future virions.

Olgotrelvir also appears to inhibit cathepsin L (CTSL), a protein implicated in facilitating viral entry of SARS-CoV-2 into the host cell.

Clinical trials
In September 2023, the drug's developer, Sorrento Therapeutics, announced top-line data that olgotrelvir had met its primary endpoints in a phase III clinical trial that enrolled 1,212 patients with mild or moderate COVID-19. The drug appeared to shorten the recovery time of 11 COVID-19 symptoms in olgotrelvir-treated patients by 2.4 days on average compared to patients in the placebo group. The drug was also shown to reduce the viral load at day 4 in treated patients compared to the placebo group. Side effects were mostly mild and infrequent, with the most common being nausea (1.5% vs. 0.2%) and skin rash (3.3% vs. 0.3%), which occurred more often in the olgotrelvir group.