| Revue: | Genetics and molecular biology |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000459254 |
| ISSN: | 1415-4757 |
| Autores: | Akbulut, Ekrem1 |
| Instituciones: | 1Malatya Turgut Ozal University, Faculty of Engineering and Natural Sciences, Malatya. Turquía |
| Año: | 2022 |
| Volumen: | 45 |
| Número: | 2 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Analítico, descriptivo |
| Resumen en inglés | 3CLpro of SARS-CoV-2 is one of the enzymes required for the replication process of the virus responsible for the COVID-19 pandemic. In this study, changes in protein stability and substrate affinity caused by mutations were investigated to stir the development of potent inhibitors. Sequence data of samples were obtained from the NCBI Virus database. Mutation analyses were performed with RDP4 and MegaX. 3CLpro tertiary models were created using Robetta. Molecular docking for peptidomimetic substrate and inhibitor ligand was done with Autodock v4.2 and Haddock v2.4. Protein stability analysis was performed using mCSM stability and DynaMut2. Twenty-four missense mutations in 3CLpro were identified in this study. Changes in the 3CLpro structure induced by the mutations Met49Thr, Leu167Ser, and Val202Ala resulted in significant levels of instability (-2.029,-2.612,-2.177 kcal.mol-1, respectively). The lowest interaction energy for substrate was -58.7 kcal.mol-1 and -62.6 kcal.mol-1 in wild-type and mutant, respectively. The lowest docking energy for ligand was -6.19 and -9.52 kcal.mol-1 for wild-type and mutant, respectively. This study reports for the first time that mutations cause increased substrate affinity of 3CLpro from SARS-CoV-2. This research provides important data for the development of potent peptidomimetic inhibitors for the treatment of COVID-19 |
| Disciplinas: | Biología, Química |
| Palabras clave: | Virus, Bioquímica, Proteínas, Proteasas, SARS-CoV-2, Mutaciones |
| Keyword: | Virus, Biochemistry, Proteins, Proteases, Mutations, SARS-CoV-2 |
| Texte intégral: | Texto completo (Ver HTML) Texto completo (Ver PDF) |
