Study of HIV-1 reverse transcriptase and protease inhibition by mushroom extracts

Abstract

Human immunodeficiency virus type-1 (HIV-1) can cause acquired immunodeficiency syndrome (AIDS), a world serious public health problem. HIV-1 protease (HIV-1 PR) and reverse transcriptase (HIV-1 RT) are necessary target enzymes which have been used for antiretroviral drugs development. Herein, Lignosus rhinocerus (LR), Auricularia polytricha (AP) and Astraeus spp. (AH) crude extracts were screened for inhibitory activities on both enzymes. Crude hexane extract of AP (APH) exhibited significant inhibition on both HIV-1 PR and RT activities not only in an in vitro non-cell based but also cell based assays. In HIV-1 infected MOLT-4 cell model, APH significantly reduced capsid protein (p24) and viral DNA synthesis. Furthermore, phytochemical compounds of APH was isolated and identified by chromatography and spectroscopy techniques. We found four major compounds, including two triacylglycerols, linoleic acid and ergosterol. Moreover, ergosterol, linoleic acid, oleic acid and palmitic acid showed significant inhibition of p24 production in the infected cells. In silico analysis by CDOCKER method supported that all candidate compounds displayed interaction with specific sites of HIV-1 PR. These results suggest that AP could be a good source of fatty acid and ergosterol which have anti-HIV-1 properties by blocking HIV-1 PR. These data would be a beneficial information for antiretroviral drug development furthermore.