title: Natural Product Kuwanon-L Inhibits HIV-1 Replication through Multiple Target Binding.
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.
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Martini
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042, Monserrato, Cagliari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042, Monserrato, Cagliari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Corona
authors.affiliation: Laboratory of Microbiology, San Raffaele Hospital, IRCCS, Via Olgettina 58, 20132, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ferrarese
authors.affiliation: Department of Biotechnology and Life Sciences, University of Insubria, Via Ravasi 2, 21100, Varese, Italy.
authors.forename: Elisa Rita
authors.initials: ER
authors.lastname: Ceresola
authors.affiliation: Laboratory of Microbiology, San Raffaele Hospital, IRCCS, Via Olgettina 58, 20132, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Visconti
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tintori
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbieri
authors.affiliation: Department of Chemistry and Technology of Drugs, University of Rome "Sapienza", Piazzale Aldo Moro 5, 00185, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calcaterra
authors.affiliation: Department of Chemistry and Technology of Drugs, University of Rome "Sapienza", Piazzale Aldo Moro 5, 00185, Roma, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iovine
authors.affiliation: Laboratory of Microbiology, San Raffaele Hospital, IRCCS, Via Olgettina 58, 20132, Milan, Italy.|Department of Biotechnology and Life Sciences, University of Insubria, Via Ravasi 2, 21100, Varese, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Canducci
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, SS 554, 09042, Monserrato, Cagliari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Tramontano
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.|Lead Discovery Siena s.r.l., Via Vittorio Alfieri 31, 53019, Castelnuovo Berardenga, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Botta
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D016503:Drug Delivery Systems; D044947:Flavonolignans / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D044947:Flavonolignans; C000611437:kuwanon-L
keywords: HIV-1 RNase H; antiviral agents; inhibitors; kuwanon-L; multiple target binding