Introduction:
K-41A is a known compound with antibacterial activity against gram-positive bacteria and coccidia. In our screening of anti-HIV compounds, we found polyether antibiotic K-41A and its analogue K-41Am isolated from a marine-derived Streptomyces sp. SCSIO 01680 exhibited anti-HIV activity.

Material and methods:
In this study, we characterised the anti-HIV activity of K-41A and K-41Am as well as the mechanism(s) involved. The dose-dependent inhibitory effects of K-41A and K-41Am on HIV-1 replication were observed in the TZM-bl-HIV-1IIIB system, MT-2-HIV-1IIIB system, and peripheral blood mononuclear cells (PBMCs)-HIV-1BaL system. The 50% inhibitory concentrations (IC50) of K-41A on HIV-1 replication in three systems were 0.75 µM, 0.09 µM, and 0.13 µM, respectively, and the selective indexes (SIs) were 5.81, 49.44, and 598.00, respectively. The IC50 of K-41Am in three systems were 5.57 µM, 0.24 µM, and 1.15 µM, respectively, and the SIs were > 1.04, 80.71, and > 5.03, respectively.

Results:
Mechanism research demonstrates that two compounds inhibited the activities of HIV-1 reverse transcriptase (RT) and integrase (IN) in a dose-dependent manner. Molecular docking shows that the docking scores were relatively high between the compound and HIV-1 RT or IN.

Conclusions:
K-41A and K-41Am possess anti-HIV-1 activity via a multi-target inhibition mechanism, which provides a novel molecular pattern for anti-HIV drug design and structural modification to improve the anti-HIV activity.