An analysis of inhibition of the severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase by zinc ion: an in silico approach

Zoghi, Sina; Khamirani, Hossein Jafari; Dastgheib, Seyed Alireza; Dianatpour, Mehdi; Ghaffarieh, Alireza

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.