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Structural basis for repurposing a 100-years-old drug suramin for treating COVID-19

By Wanchao Yin, Xiaodong Luan, Zhihai Li, Leike Zhang, Ziwei Zhou, Minqi Gao, Xiaoxi Wang, Fulai Zhou, Jingjing Shi, Erli You, Mingliang Liu, Qingxia Wang, Qingxing Wang, Yi Jiang, Hualiang Jiang, Gengfu Xiao, Xuekui Yu, Shuyang Zhang, H. Eric Xu

Posted 06 Oct 2020
bioRxiv DOI: 10.1101/2020.10.06.328336

The COVID-19 pandemic by non-stop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report the discovery of suramin, a 100-year-old drug, as a potent inhibitor of the SARS-CoV-2 RNA dependent RNA polymerase (RdRp) through 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 COVID-19. The 2.6 Å cryo-EM structure of the viral RdRp bound to suramin reveals two binding sites of suramin, with one site directly blocking the binding of the RNA template strand and the other site clash with the RNA primer strand near the RdRp catalytic active site, therefore inhibiting the viral RNA replication. Furthermore, suramin potently inhibits SARS-CoV-2 duplication in Vero E6 cells. These results provide a structural mechanism for the first non-nucleotide inhibitor of the SARS-CoV-2 RdRp and a rationale for repurposing suramin for treating COVID-19. ### Competing Interest Statement The authors have declared no competing interest.

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