| Title | From the traditional Chinese medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors |
|---|---|
| Author | Lijia Xu1, Nicole Grandi2, Claudia Del Vecchio3, Daniela Mandas2, Angela Corona2, Dario Piano2, Francesca Esposito2*, Cristina Parolin3, and Enzo Tramontano2 |
| Address | 1Institute of Medicinal Plant Development (IMPLAD), 151 Malianwa North Road Haidian District, 100193 Beijing, P. R. China, 2Department of Life and Environmental Sciences, University of Cagliari, Cittadella di Monserrato SS554, 09042, Monserrato, Cagliari, Italy, 3Department of Molecular Medicine, University of Padova, via Gabelli 63, 35121 Padova, Italy |
| Bibliography | Journal of Microbiology, 53(4),288-293, 2015, |
| DOI | 10.1007/s12275-015-4652-0 |
| Key Words | Schisandra chinensis, HIV-1, reverse transcriptase, plant extracts, plant diversity, HIV resistance |
| Abstract | HIV-1 reverse transcriptase (RT) is still an extremely attractive pharmaceutical target for the identification of new inhibitors possibly active on drug resistant strains. Medicinal plants are a rich source of chemical diversity and can be used to identify novel scaffolds to be further developed by chemical modifications. We investigated the ability of the main lignans from Schisandra chinensis (Turcz.) Baill. fruits, commonly used in Traditional Chinese Medicine, to affect HIV-1 RT functions. We purified 6 lignans from Schisandra chinensis fruits and assayed their effects on HIV-1 RT and viral replication. Among the S. chinensis fruit lignans, Schisandrin B and Deoxyschizandrin selectively inhibited the HIV-1 RTassociated DNA polymerase activity. Structure activity relationship revealed the importance of cyclooctadiene ring substituents for efficacy. In addition, Schisandrin B was also able to impair HIV-1 RT drug resistant mutants and the early phases of viral replication. We identified Schisandrin B and Deoxyschizandrin as new scaffold for the further development of novel HIV-1 RT inhibitors. |