AVI-4206 is a selective Mac1 inhibitor with an IC50 of 64 nM for inhibiting Mac1's catalytic activity. It effectively reduces SARS-CoV-2 viral replication, restores interferon response, and demonstrates survival benefits in animal models infected with SARS-CoV-2. AVI-4206 is applicable for research related to SARS-CoV-2 infections.

AVI-4206 inhibits the catalytic activity of Mac1 in PARP10 self-ADP-ribosylation and coupled NudT5/AMP-Glo assays, with an IC50 of 64 nM within concentrations of 0.1-1000000 nM. It binds with high efficiency and selectivity to Mac1 in A549 cells at 10 μM. However, AVI-4206 shows limited efficacy in SARS-CoV-2 infected Vero-TMPRSS2 or A549-ACE2h cells at concentrations ranging from 0.01-10000 nM. In addition, AVI-4206 at concentrations of 0.16-100 μM over 24-72 hours reduces viral particle production following infection by a Mac1 deletion virus (WA1 N40D mutant).

AVI-4206, administered intraperitoneally at a dose of 100 mg/kg twice daily for 7 consecutive days, demonstrates efficacy in the K18-hACE2 mouse model of SARS-CoV-2 infection.