In silico exploration through molecular docking and molecular dynamics of some cinnamoyl substituted compounds on targets related to SARS-CoV-2

Resumen

The pandemic unleashed by the emergence of a new strain of the SARS-CoV-2 coronavirus in late 2019, has created significant pressure on health teams and research centers to find effective treatments that can lessen the effects of this disease on the most severe patients. Different strategies have been used in medicinal chemistry, including the repositioning of approved drugs with different indications in the clinic, the reevaluation of experimental molecules, and in silico studies. Because the disease does not currently have a vaccine or clinically proven treatment, we decided in this study to design and evaluate using both molecular coupling and molecular dynamics simulations, some potential ligands towards four critical enzymes in the virus replication cycle, based on structural characteristics of other compounds with demonstrated pharmacological activity against previous SARS-CoV and MERS deseases, which pathological agents are coronavirus strains closely related to SARS-CoV-2. The results suggest that some hydroxylated ligands capable of adopting a V-like conformation could have a good affinity in Mpro and PLpro proteases and possess antioxidant and anti-inflammatory capacities so that they could be the basis of future research projects for the development of new antivirals.