Inhibitory Effect of Lithospermic Acid on the HIV-1 Nucleocapsid Protein

被引:6
作者
Mori, Mattia [1 ]
Ciaco, Stefano [1 ,2 ]
Mely, Yves [2 ]
Karioti, Anastasia [3 ]
机构
[1] Univ Siena, Dept Biotechnol Chem & Pharm, Via Aldo Moro 2, I-53100 Siena, Italy
[2] Univ Strasbourg, Fac Pharm, UMR CNRS 7021, Lab Bioimagerie & Pathol, 74 Route Rhin, F-67401 Illkirch Graffenstaden, France
[3] Aristotle Univ Thessaloniki, Sch Pharm, Lab Pharmacognosy, Thessaloniki 54124, Greece
来源
MOLECULES | 2020年 / 25卷 / 22期
关键词
lithospermic acid; nucleocapsid protein; catechol; natural products; HIV; molecular modeling; fluorescence-based assays; STRUCTURAL-CHARACTERIZATION; IDENTIFICATION; COMPLEX; POTENT; INTEGRATION; TARGET; NCP7;
D O I
10.3390/molecules25225434
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The HIV-1 nucleocapsid protein (NC) is a desirable target in antiretroviral therapy due to its high conservation among HIV-1 strains, and to its multiple and crucial roles in the HIV-1 replication cycle. Natural products represent a valuable source of NC inhibitors, with the catechol group being a privileged scaffold in NC inhibition. By coupling molecular modeling with NMR spectroscopy and fluorescence-based assays, we disclosed lithospermic acid, a catechol derivative extracted from Salvia miltiorrhizza, as a potent and chemically stable non-covalent inhibitor of the NC. Being different from other catechol derivative reported so far, lithospermic acid does not undergo spontaneous oxidation in physiological conditions, thus becoming a profitable starting point for the development of efficient NC inhibitors.
引用
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页数:11
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