Evaluation of the inhibitory potential of bioactive compounds against SARS-CoV-2 by in silico approach

Abstract

The COVID-19 (Coronavirus Disease 19) pandemic brought on by the SARS-CoV2 outbreak (Severe Acute Respiratory Syndrome Coronavirus 2) has stimulated the exploration of various available chemical compounds that could be used to treat the infection. This has driven numerous researchers to investigate the antiviral potential of several bioactive compounds from medicinal plants due to their reduced adverse effects compared to chemicals. Some of the bioactive compounds used in folklore treatment strategies are reported as effective inhibitors against the proliferative and infective cycles of SARS-CoV2. The secondary metabolites from plants are generally used to treat various diseases due to their intact medicinal properties. The present study analyses the inhibitory potential of phytocompounds from medicinal plants like Sphaeranthus indicus, Lantana camara and Nelumbo nucifera against SARS-CoV2 by molecular docking. Ten druggable protein targets from SARS-CoV2 are docked against the phytocompounds from the selected medicinal plants. The phytocompounds Astragalin, Isoquercetin, and 5-hydroxy-7-methoxy-6-c-glycosy avone were found to have lower binding energy depicting their inhibitive potential compared with the reported inhibitors that are used in the treatment of SARS-CoV2 infection. To assess the compounds' potential as drugs, their ADMET characteristics were also examined. Sphaeranthus indicus, Lantana camara, Nelumbo nucifera six possible compounds were separately screened for ADME and toxicity characteristics, then the results were analyzed.Microsecond-level molecular dynamics simulations of both the ligands complexed with NSP15 revealed that the ligand induces allosteric effects on NSP15, which could lead to destabilization of NSP15 hexameric interface and loss of RNA binding. HighlightsExploration of anti-viral properties of bioactive compounds from Sphaeranthus indicus, Lantana camara and Nelumbo nucifera.Phytocompounds with medicinal properties used in primordial treatment options are considered for the study.Molecular docking revealed compounds with the ability to inhibit the replication and breakage of polyprotein in the SARS-CoV2 virus.Molecular dynamic simulation of NSP15 with the ligand showed the binding of ligand might lead to loss of RNA binding.