Jun8-76-3A is a potent, highly selective noncovalent SARS-CoV-2 main protease (Mpro) inhibitor with IC50 of 0.2 uM.
Jun8-76-3A also comparably and potently inhibits SARS-CoV Mpro with IC50 of 0.27 uM, does not inhibit papain-like protease (PLpro, IC50>20 uM).
Jun8-76-3A selectively inhibited SARS-CoV-2 Mpro and SARS-CoV Mpro with high potency but not other viral proteases (MERS-CoV Mpro, HCoV-OC43 Mpro, EV-A71 3Cpro, EV-D68 3Cpro, EV-A71 2Apro, EV-D68 2Apro, and SARS-CoV-2 PLpro), which was similar to ML188, Jun8-76-3A only showed weak inhibition against calpain 1 and cathepsin L with IC50 of 6.00 μM and 10.5 μM, respectively, corresponding to selectivity indexes of 40 and 70 with regard to SARS-CoV-2 Mpro inhibition.
Jun8-76-3A demobnstrated high cellular antiviral activity against SARS CoV-2 (USA-WA1/2020 isolate) in Vero E6 cells with EC50 of 1.27 uM, without cytotoxicity (CC50>100 uM), which is similar to the antiviral potency of the covalent inhibitor GC376 (EC50=1.51 uM).
Jun8-76-3A is highly selective compared to the covalent inhibitor GC376.