Key result
In silico analysis predicted that Zn(2+) inhibits SARS-CoV-2 RNA-dependent RNA polymerase by binding to the active aspartic acid triad (618D, 760D, and 761D).
Why the study?
Zinc ion is a reported inhibitor of SARS-CoV, prompting the hypothesis that it may similarly inhibit the newly discovered SARS-CoV-2.
Does Zn2+ bind to and inhibit SARS-CoV-2 RNA-dependent RNA polymerase in silico?
Does Zn2+ bind to and inhibit SARS-CoV-2 RNA-dependent RNA polymerase in silico?
In silico modeling suggests zinc ions may inhibit SARS-CoV-2 RNA-dependent RNA polymerase by binding to its active aspartic acid triad.
Background: Coronavirus disease 2019 is caused by exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was reported that Zn(2+) is an inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV). We hypothesize that the same applies to the newly discovered SARS-CoV-2. Material & methods: We compared the structure of RNA-dependent RNA polymerase between SARS-CoV and SARS-CoV-2. The RdRp’s binding to Zn(2+) was studied by metal ion-binding site prediction and docking server. Results: Several regions containing key residues were detected. The functional aspartic acid residues RdRp, 618D, 760D and 761D were among the predicted Zn(2+)-binding residues. Conclusion: The most probable mechanism of inhibition of RdRp by Zn(2+) is binding to the active aspartic acid triad while other binding sites can further destabilize the enzyme or interfere with the fidelity-check mechanism.
No takes yet. Share an insight, caveat, or question.
Zoghi et al. (2021) studied Coronavirus disease 2019 (SARS-CoV-2). Zinc ion (Zn2+) was evaluated on Zn(2+)-binding residues on RNA-dependent RNA polymerase. In silico analysis predicted that Zn(2+) inhibits SARS-CoV-2 RNA-dependent RNA polymerase by binding to the active aspartic acid triad (618D, 760D, and 761D).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: