Natural Product Kuwanon-L Inhibits HIV-1 Replication through Multiple Target Binding

Author(s)
Riccardo Martini, Francesca Esposito, Angela Corona, Roberto Ferrarese, Elisa Rita Ceresola, Laura Visconti, Cristina Tintori, Alessandro Barbieri, Andrea Calcaterra, Valentina Iovine, Filippo Canducci, Enzo Tramontano, Maurizio Botta
Abstract

In recent years many advances have been made in the fight against HIV-1 infection. However, the lack of a vaccine, together with the increasing resistance to the highly active anti-retroviral therapy (HAART), make HIV-1 infection still a serious global emergency. Thus, new compounds with original modes of action are continuously required, and natural products have ever been a very interesting class of pharmacologically active molecules. Some of them have been used since ancient times against viral infections. Here we present a work in which we suggest that kuwanon-L, a natural product active as an HIV-1 integrase (IN) inhibitor, might exert its overall antiviral activity through binding to multiple viral targets. Specific enzymatic tests, together with a time-of-addition (TOA) experiment, support our hypothesis of binding both to IN and to reverse transcriptase (RT). Overall, this compound can be considered an attractive lead for the development of new classes of antiviral agents able to overcome the problem of resistance, due to its ability to exert its action by binding simultaneously to multiple viral targets.

Organisation(s)
Department of Pharmaceutical Chemistry
Journal
ChemBioChem: a european journal of chemical biology
Volume
18
Pages
374-377
No. of pages
4
ISSN
1439-4227
DOI
https://doi.org/10.1002/cbic.201600592
Publication date
02-2017
Publication status
Published
Peer reviewed
Yes
Austrian Fields of Science 2012
301207 Pharmaceutical chemistry
Keywords
Anti-HIV Agents/chemistry, Cell Line, Drug Delivery Systems, Flavonolignans/chemistry, HIV-1/drug effects, Humans, Molecular Structure, Virus Replication/drug effects
Portal url
https://ucris.univie.ac.at/portal/en/publications/natural-product-kuwanonl-inhibits-hiv1-replication-through-multiple-target-binding(2daf58b4-b7a6-48e7-9edf-88c0ebe86c85).html