RT Journal Article
T1 In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against Mpro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature.
A1 Mejias, Francisco J R
A1 Duran, Alexandra G
A1 Chinchilla, Nuria
A1 Varela, Rosa M
A1 Alvarez, Jose A
A1 Molinillo, Jose M G
A1 Garcia-Cozar, Francisco
A1 Macias, Francisco A
K1 COVID-19
K1 SARS-CoV-2
K1 Benzoxazinoid
K1 Docking
K1 Molecular dynamics
K1 Sesquiterpene
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 Mpro, 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 Å. 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
YR 2022
FD 2022-08-29
LK http://hdl.handle.net/10668/21594
UL http://hdl.handle.net/10668/21594
LA en
NO Mejías FJR, Durán AG, Chinchilla N, Varela RM, Álvarez JA, Molinillo JMG, et al. In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against Mpro, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature. Toxins (Basel). 2022 Aug 29;14(9):599
NO This paper is affectionately dedicated in the memory of Mariola Macías (1984–2020) on her second anniversary. She was an excellent professional, an emergency doctor at Hospital Punta Europa, Algeciras (Cadiz), Spain, a Doctor in Immunology and, above all, a great person. She worked intensively not only in clinical functions but also in research against SARS- CoV-2 and was passionate about Natural Products. Her humanity, kindness, special and unmistakable smile, generosity, dedication and professionalism will never be forgotten. All simulations were performed using computational facilities at the ‘Servicio de Supercomputación of Área de Sistemas de Información′ of the University of Cádiz. F.J.R.M thanks Iván Carrillo-Berdugo for his MD comments and advice.
DS RISalud
RD Apr 19, 2025