Inhibition of HIV-1 Replication by Secondary Metabolites From Endophytic Fungi of Desert Plants



Brian P. Wellensiek1, +, Rajesh Ramakrishnan1, ++, Bharat P. Bashyal2, Yvette Eason1, A. A. Leslie Gunatilaka2, Nafees Ahmad*, 1
1 Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
2 Southwest Center for Natural Products Research and Commercialization, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ 85724, USA


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© Wellensiek et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http: //creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; TeL: 520-626-7022; Fax: 520-626-2100; E-mail: nafees@u.arizona.edu
+ Present address: The Biodesign Institute at Arizona State University, Tempe, AZ, USA
++ Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA


Abstract

Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication.

Keywords: : Drug discovery, endophytic fungi, HIV-1, secondary metabolites..