Exploring the Catalytic Mechanism of the RNA Cap Modification by nsp16-nsp10 Complex of SARS-CoV-2 through a QM/MM Approach
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Altres documents de l'autoria: Araújo Silva, José Rogério; Urban, Jaime; Araújo, Edson; Lameira, Jerônimo; Moliner, Vicent; Nahum Alves, Cláudio
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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 ApproachAutoria
Data de publicació
2021-12-28Editor
MDPIISSN
1422-0067Cita bibliogràfica
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/ijms23010300Tipus de document
info:eu-repo/semantics/articleVersió
info:eu-repo/semantics/publishedVersionParaules clau / Matèries
Resum
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 ... [+]
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. [-]
Publicat a
International Journal of Molecular Sciences, Vol. 23 (2022)Entitat finançadora
National Council for Scientific and Technological Development
Codi del projecte o subvenció
CNPq grant 402572/2018-1
Drets d'accés
info:eu-repo/semantics/openAccess
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