Antiviral agent 80

Antiviralagent 80 is a Zanamivir-Amantadine conjugate that acts as a dual inhibitor of the influenza virus M2 ion channel and neuraminidase (NA). It demonstrates potent inhibitory activity against both wild-type and drug-resistant influenza neuraminidase mutants, with IC50 values ranging from 1.50 nM to 120.4 nM. Antiviralagent 80 is applicable for influenza-related research.

Antiviral agent 80 (Compound 7j) exhibits potent inhibitory activity against both wild-type and drug-resistant influenza neuraminidase (NA) mutants, with IC50 values ranging from 1.50 nM to 120.4 nM, specifically 1.5, 1.69, and 2.05 nM for N9, N1, and N1 (H275Y) respectively. It protects MDCK cells from influenza A virus-induced cytopathic effects with EC50 values between 11.13 nM and 12.55 nM, and a CC50 greater than 200 μM, indicating high selectivity. At a concentration of 5 μM for 24 hours, Antiviral agent 80 induces proteasome-dependent degradation of NA in NA plasmid-transfected HEK293T cells, reaching a degradation rate of approximately 95%, without upregulating autophagy markers in BEAS-2B, HEK293T, or A549 cells. It efficiently penetrates cell membranes and accumulates in MDCK cells, with intracellular retention rates of 88.8% and 19.1% at pretreatment concentrations of 100 μM and 25 μM, respectively. After washing out extracellular compound, its EC50 against A/WSN/1933 slightly increases from 11.13 nM to 48.0 nM, demonstrating strong intracellular antiviral activity. Antiviral agent 80 inhibits multiple stages of the influenza A virus life cycle in MDCK cells, as evidenced by the reduction in M1 protein levels.