Olgotrelvir (STI-1558) is a next-generation antiviral targeting SARS-CoV-2 Mpro and host lysosomal cysteine protease cathepsin L (CTSL) with high antiviral activity, Olgotrelvir is the prodrug of AC1115.
Olgotrelvir (STI-1558) is readily converted to its active form AC1115 in biorelevant media and human blood.
Olgotrelvir (STI-1558) shows a covalent linkage between the aldehyde warhead and the sulfur atom of C145 at the Mpro catalytic active site.
Olgotrelvir (STI-1558) displays antiviral activity against SARS-CoV-2 VOCs in Vero E6 cells, including WA-1, Alpha, Beta, Delta, Lambda, and Gamma variants with EC50 of 0.28-4.26 uM, without cytotoxicity up to 100 uM.
Olgotrelvir (STI-1558) displays antiviral effects in the EpiAirway system composed of differentiated normal human bronchial epithelial cells (dNHBE) with EC50 of <41 nM.
Olgotrelvir (STI-1558) (1,000 mg/kg, BID, p.o.) significantly reduces viral RNA shedding, exhibits strong in vivo antiviral activity in K18-hACE2 transgenic mice.
Olgotrelvir (STI-1558) preventsmice from weight loss caused by SARS-CoV-2 infection and blocks pro-inflammatory cytokine release.