In Vitro Inhibitory Effects of the Herbal-Marine Compound HESA-A Against Replication of Human Immunodeficiency Virus-1

For more than 2 decades, human immunodeficiency virus (HIV) infectionhas been known to cause significant morbidity and mortality. Difficulties in treatingHIV-infected patients include adverse effects and drug resistance and continue to limitthe use of conventional anti-retroviral therapies. To find new anti-retroviral drugs from natural sources, we investigated theinhibitory effects and mechanism of action of HESA-A, a natural biological compound ofherbal-marine origin, against HIV-1 replication in vitro. In this study, we used a single-cycle replicable HIV-1 system inwhich co-transfection of human embryonic kidney (HEK)-293T cells with pmzNL4-3,psPAX2, and pM2G.2 plasmids was performed. Cytotoxicity and cytopathic protectionassays were performed using the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-(2H)-tetrazolium-5-carboxanilide method. Inhibition of p24 antigen production was analyzed, andtime-of-drug-addition assay was conducted using quantitative enzyme-linked immunosorbentassay (ELISA). HESA-A inhibited HIV-1-induced cytopathic effect in MT2 and HEK293T cells, andthe selectivity index values were 13.3 and 8, respectively. We performed quantitative p24ELISA and added varying concentrations of HESA-A in cell culture supernatants at differenttimes; we observed that HESA-A preserved its ability to inhibit viral replication evenat 12 h post-infection. These results suggest that HESA-A has potent anti-HIV activity, and its mechanismof action likely involves interference during the late stages of viral replication,such as virus maturation.