ALG-097558 is an orally active 3CL protease inhibitor. It demonstrates broad antiviral activity against various SARS-CoV-2 variants and other human coronaviruses, including SARS-CoV-1, α-HCoV 229E, and β-HCoV OC43. ALG-097558 exhibits potent inhibitory effects, with an IC50 of 2 nM for SARS-CoV-2 3CL protease and 6 nM for 229E 3CL protease. In a SARS-CoV-2 hamster infection model, ALG-097558 shows antiviral activity and can be used for research on viral infections.

ALG-097558 (Compound 7) demonstrates significant inhibitory activity with an IC50 of 2 nM against the SARS-CoV-2 3CL protease and 6 nM against the 229E 3CL protease. It exhibits powerful pan-coronavirus antiviral activity by strongly inhibiting human β-CoV OC43 (EC50 = 8 nM), SARS-CoV-1 (EC50 = 22 nM), and B.1.1.7 AS49D (EC50 = 11 nM). Additionally, ALG-097558 is effective against β MERS-CoV (IC50 = 59 nM), OC43 hCoV OC43 (IC50 = 0.6 nM), α CoV 229E (IC50 = 2.8 nM), and γ Beluga whale CoV (IC50 = 1 nM) by inhibiting their 3CL protease activity. Furthermore, ALG-097558 (0-1 μM, 4 days) suppresses the replication of SARS-CoV-2 B.1.1.7 in primary human bronchial epithelial cells (HAEC) cultured at the air-liquid interface.

When administered orally at doses of 2.5-150 mg/kg twice daily for three consecutive days, ALG-097558 (Compound 7) demonstrates antiviral activity in a SARS-CoV-2 hamster infection model when co-administered with Ritonavir.