Open AccessH ypericum hircinum L . components as new single‐molecule inhibitors of both HIV ‐1 reverse transcriptase‐associated DNA polymerase and ribonuclease H activities
Author(s) -
Esposito Francesca,
Sanna Cinzia,
Del Vecchio Claudia,
Cannas Valeria,
Venditti Alessandro,
Corona Angela,
Bianco Armandodoriano,
Serrilli Anna M.,
Guarcini Laura,
Parolin Cristina,
Ballero Mauro,
Tramontano Enzo
Publication year - 2013
Publication title -
pathogens and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.983
H-Index - 105
ISSN - 2049-632X
DOI - 10.1111/2049-632x.12051
Subject(s) - betulinic acid , reverse transcriptase , rnase h , dna polymerase , biology , biochemistry , enzyme , rna , genetics , gene
Among HIV ‐1 reverse transcriptase ( RT )‐associated functions, DNA polymerase and R ibonuclease H ( RN ase H ) are both essential for HIV replication and excellent targets for drug development. While all RT inhibitors approved for therapy target the DNA polymerase activity, there is the pressing need for new RT inhibitors possibly targeting the RN ase H function. In the last 20 years, many natural substances have shown antiviral activity against HIV ‐1, but only a few against the RN ase H function. In this study, we have tested the ethanolic extracts obtained by the H ypericum hircinum L . ( H ypericaceae ) growing in S ardinia ( I taly) on the HIV ‐1 RT ‐associated RN ase H function and found that they have inhibitory effects. Active extracts were fractionated up to obtain the main components that have been isolated, tested, and identified to be betulinic acid, shikimic acid, chlorogenic acid, quercetin, 5,7,3′,5′‐tetrahydroxyflavanone, and 5,7,3′,5′‐tetrahydroxyflavanone 7‐ O ‐glucoside. B etulinic acid and 5,7,3′,5′‐tetrahydroxyflavanone 7‐ O ‐glucoside were active on both RT ‐associated activities, and betulinic acid was also active on HIV ‐1 mutant RT s resistant to efavirenz. Overall, our results suggest that some of these compounds inhibit the HIV ‐1 RT binding to an allosteric site previously described for other natural compounds and are potential leads for further drug development of a single molecules having dual inhibitory activity.