7D4F

Structure of COVID-19 RNA-dependent RNA polymerase bound to suramin

Summary for 7D4F

• Entry DOI: 10.2210/pdb7d4f/pdb
• EMDB information: 30572
• Descriptor: Non-structural protein 8, Non-structural protein 7, RNA-directed RNA polymerase, ... (5 entities in total)
• Functional Keywords: covid-19, rna polymerase, suramin binding, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 4
• Total formula weight: 162815.84

Authors

Li, Z.,Yin, W.,Zhou, Z.,Yu, X.,Xu, H. (deposition date: 2020-09-23, release date: 2020-11-11, Last modification date: 2024-03-27)

Primary citation

Yin, W.,Luan, X.,Li, Z.,Zhou, Z.,Wang, Q.,Gao, M.,Wang, X.,Zhou, F.,Shi, J.,You, E.,Liu, M.,Wang, Q.,Jiang, Y.,Jiang, H.,Xiao, G.,Zhang, L.,Yu, X.,Zhang, S.,Eric Xu, H.
Structural basis for inhibition of the SARS-CoV-2 RNA polymerase by suramin.
Nat.Struct.Mol.Biol., 28:319-325, 2021

PubMed 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.

PubMed: 33674802
DOI: 10.1038/s41594-021-00570-0

Experimental method

ELECTRON MICROSCOPY (2.57 Å)