| Literature DB >> 33674802 |
Wanchao Yin1, Xiaodong Luan2,3,4, Zhihai Li1,5, Ziwei Zhou1,5,6, Qingxing Wang6,7, Minqi Gao8, Xiaoxi Wang1, Fulai Zhou1, Jingjing Shi1, Erli You1, Mingliang Liu1, Qingxia Wang1,5, Yi Jiang1,6, Hualiang Jiang1,6, Gengfu Xiao7, Leike Zhang9,10, Xuekui Yu11,12,13, Shuyang Zhang14,15,16, H Eric Xu17,18.
Abstract
The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.Entities:
Year: 2021 PMID： 33674802 DOI： 10.1038/s41594-021-00570-0
Source DB: PubMed Journal: Nat Struct Mol Biol ISSN： 1545-9985 Impact factor: 15.369