El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / SARS-CoV-2 main protease is a common target for inhibition assays due to its high conservation among coronaviruses. Since flavonoids show antiviral activity, several in silico works have proposed them as potential SARS-CoV-2 main protease inhibitors. Nonetheless, there is reason to doubt certain results given the lack of consideration for flavonoid promiscuity or main protease plasticity, usage of short library sizes, absence of control molecules and/or the limitation of the methodology to a single target site. Here, we report a virtual screening study where dorsilurin E, euchrenone a11, sanggenol O and CHEMBL2171598 are proposed to inhibit main protease through different pathways. Remarkably, novel structural mechanisms were observed after sanggenol O and CHEMBL2171598 bound to experimentally proven allosteric sites. The former drastically affected the active site, while the latter triggered a hinge movement which has been previously reported for an inactive SARS-CoV main protease mutant. The use of a curated database of 4.8 k flavonoids, combining two well-known docking software (AutoDock Vina and AutoDock4.2), molecular dynamics and MMPBSA, guaranteed an adequate analysis and robust interpretation. These criteria can be considered for future screening campaigns against SARS-CoV-2 main protease. / Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica / Revisión por pares
| Identifer | oai:union.ndltd.org:PERUUPC/oai:repositorioacademico.upc.edu.pe:10757/657336 |
| Date | 01 December 2021 |
| Creators | Jiménez-Avalos, Gabriel, Vargas-Ruiz, A. Paula, Delgado-Pease, Nicolás E., Olivos-Ramirez, Gustavo E., Sheen, Patricia, Fernández-Díaz, Manolo, Quiliano, Miguel, Zimic, Mirko, Agurto-Arteaga, Andres, Antiparra, Ricardo, Ardiles-Reyes, Manuel, Calderon, Katherine, Cauna-Orocollo, Yudith, de Grecia Cauti-Mendoza, Maria, Chipana-Flores, Naer, Choque-Guevara, Ricardo, Chunga-Girón, Xiomara, Criollo-Orozco, Manuel, De La Cruz, Lewis, Delgado-Ccancce, Elmer, Elugo-Guevara, Christian, Fernández-Sanchez, Manolo, Guevara-Sarmiento, Luis, Gutiérrez, Kristel, Heredia-Almeyda, Oscar, Huaccachi-Gonzalez, Edison, Huerta-Roque, Pedro, Icochea, Eliana, Isasi-Rivas, Gisela, Juscamaita-Bartra, Romina A., Licla-Inca, Abraham, Montalvan, Angela, Montesinos-Millan, Ricardo, Núñez-Fernández, Dennis, Ochoa-Ortiz, Adiana, Páucar-Montoro, Erika, Pauyac, Kathy, Perez-Martinez, Jose L., Perez-M, Norma, Poma-Acevedo, Astrid, Quiñones-Garcia, Stefany, Ramirez-Ortiz, Ingrid, Ramos-Sono, Daniel, Rios-Angulo, Angela A., Rios-Matos, Dora, Rojas-Neyra, Aldo, Romero, Yomara K., Salguedo-Bohorquez, Mario I., Sernaque-Aguilar, Yacory, Soto, Luis F., Tataje-Lavanda, Luis, Ticona, Julio, Vallejos-Sánchez, Katherine, Villanueva-Pérez, Doris, Ygnacio-Aguirre, Freddy |
| Publisher | Nature Research |
| Source Sets | Universidad Peruana de Ciencias Aplicadas (UPC) |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/article |
| Format | application/html |
| Source | Universidad Peruana de Ciencias Aplicadas (UPC), Repositorio Academico - UPC, Scientific Reports, 11, 1 |
| Rights | info:eu-repo/semantics/embargoedAccess |
| Relation | https://www.nature.com/articles/s41598-021-94951-6 |
Page generated in 0.0035 seconds