RT journal article
T1 In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M-pro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature
A1 Rodríguez Mejías, Francisco Javier
A1 García Durán, Alexandra
A1 Chinchilla Salcedo, Nuria
A1 Varela Montoya, Rosa María
A1 Álvarez Saura, José Ángel
A1 González Molinillo, José María
A1 García Cózar, Francisco José
A1 Macías Domínguez, Francisco Antonio
A2 BiomedicinaBiotecnología y Salud Pública
A2 Química Física
A2 Química Orgánica
K1 molecular dynamics
K1 docking
K1 SARS-CoV-2
K1 COVID-19
K1 sesquiterpene
K1 benzoxazinoid
AB In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3H-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski's rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3H-phenoxazin-3-one are able to generate more hydrogen bonds with the M-pro, thus enhancing the stability of the protein-ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 angstrom. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2.
PB MDPI
SN 2072-6651
YR 2022
FD 2022-09
LK http://hdl.handle.net/10498/28314
UL http://hdl.handle.net/10498/28314
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 08-nov-2026