Department of Biotechnology, Chemistry and Pharmacy, University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch, France.
Molecules. 2020 Nov 20;25(22):5434. doi: 10.3390/molecules25225434.
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 , 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.
HIV-1 核衣壳蛋白（NC）是抗逆转录病毒治疗的一个理想靶点，因为它在 HIV-1 株之间高度保守，并且在 HIV-1 复制周期中具有多种关键作用。天然产物是 NC 抑制剂的一个有价值的来源，儿茶酚基团是 NC 抑制的一个优势结构。通过将分子建模与 NMR 光谱和基于荧光的测定法相结合，我们揭示了来自 的丹参素酸，一种儿茶酚衍生物，是 NC 的有效且化学稳定的非共价抑制剂。与迄今为止报道的其他儿茶酚衍生物不同，丹参素酸在生理条件下不会自发氧化，因此成为开发有效 NC 抑制剂的一个有价值的起点。
