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Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach
dc.contributor.author | Araújo Silva, José Rogério | |
dc.contributor.author | Urban, Jaime | |
dc.contributor.author | Araújo, Edson | |
dc.contributor.author | Lameira, Jerônimo | |
dc.contributor.author | Moliner, Vicent | |
dc.contributor.author | Nahum Alves, Cláudio | |
dc.date.accessioned | 2022-02-09T15:54:23Z | |
dc.date.available | 2022-02-09T15:54:23Z | |
dc.date.issued | 2021-12-28 | |
dc.identifier.citation | Silva, J.R.A.; Urban, J.; Araújo, E.; Lameira, J.; Moliner, V.; Alves, C.N. Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach. Int. J. Mol. Sci. 2022, 23, 300. https://doi.org/ 10.3390/ijms23010300 | ca_CA |
dc.identifier.issn | 1422-0067 | |
dc.identifier.uri | http://hdl.handle.net/10234/196686 | |
dc.description.abstract | The inhibition of key enzymes that may contain the viral replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have assumed central importance in drug discovery projects. Nonstructural proteins (nsps) are essential for RNA capping and coronavirus replication since it protects the virus from host innate immune restriction. In particular, nonstructural protein 16 (nsp16) in complex with nsp10 is a Cap-0 binding enzyme. The heterodimer formed by nsp16-nsp10 methylates the 50 -end of virally encoded mRNAs to mimic cellular mRNAs and thus it is one of the enzymes that is a potential target for antiviral therapy. In this study, we have evaluated the mechanism of the 20 -O methylation of the viral mRNA cap using hybrid quantum mechanics/molecular mechanics (QM/MM) approach. It was found that the calculated free energy barriers obtained at M062X/6-31+G(d,p) is in agreement with experimental observations. Overall, we provide a detailed molecular analysis of the catalytic mechanism involving the 20 -O methylation of the viral mRNA cap and, as expected, the results demonstrate that the TS stabilization is critical for the catalysis. | ca_CA |
dc.format.extent | 16 p. | ca_CA |
dc.format.mimetype | application/pdf | ca_CA |
dc.language.iso | eng | ca_CA |
dc.publisher | MDPI | ca_CA |
dc.relation.isPartOf | International Journal of Molecular Sciences, Vol. 23 (2022) | ca_CA |
dc.rights | Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | ca_CA |
dc.rights.uri | http://creativecommons.org/licenses/by-sa/4.0/ | ca_CA |
dc.subject | SARS-CoV-2 | ca_CA |
dc.subject | nsp16-nsp10 | ca_CA |
dc.subject | 20 -O methylation | ca_CA |
dc.subject | catalytic mechanism | ca_CA |
dc.subject | QM/MM | ca_CA |
dc.subject | TS stabilization | ca_CA |
dc.subject | free energy | ca_CA |
dc.title | Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach | ca_CA |
dc.type | info:eu-repo/semantics/article | ca_CA |
dc.identifier.doi | https://doi.org/10.3390/ijms23010300 | |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | ca_CA |
dc.type.version | info:eu-repo/semantics/publishedVersion | ca_CA |
project.funder.name | National Council for Scientific and Technological Development | ca_CA |
oaire.awardNumber | CNPq grant 402572/2018-1 | ca_CA |
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