Virtual Screening for the Identification of Potential Candidate Molecules Against Envelope (E) and Membrane (M) Proteins of SARS-CoV-2

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a disease currently spreading around the world. Some drugs are underway or being used to combat this disease. Several proteins of the virus can be targeted in therapeutic approaches. Two structural proteins, membrane (M), envelope (E) have critical roles in virus life cycle, such as assembly, budding, envelope formation and pathogenesis. Here, we employed the in silico strategies to identify and evaluate the selected potential compounds against M and E proteins. For this, the structures of proteins were modeled and then several groups of compounds as FDA approved, natural products or under clinical trials were screened from DrugBank and ZINC databases. The selected dockings were analyzed and the ligands with best binding affinity scores were subjected to evaluate drug-likeness and medicinal chemistry friendliness through prediction of ADMET properties. Normal mode analyses were also performed for six selected complexes to explore the collective motions of proteins. Molecular dynamic (MD) simulation was also performed to calculate the stability of two docked protein-ligand complexes. The results revealed that several compounds had high affinity to the proteins along with some acceptable profiles of mobility and deformability, especially, for M protein. The aim of this study was finding the potential compounds with inhibitory effect on membrane and envelope proteins of SARS-CoV-2 and according to the results several compounds especially some FDA-approved drugs and natural compounds shown that can be applied as hit compounds against these structural proteins of the virus.