Structure-based screening of novel lichen compounds against SARS Coronavirus main protease (Mpro) as potentials inhibitors of COVID-19

ABSTRACT: The outbreak of SARS-CoV-2 and deaths caused by it all over the world have imposed great concern on the scientific community to develop potential drugs to combat Coronavirus disease-19 (COVID-19). In this regard, lichen metabolites may offer a vast reservoir for the discovery of antiviral drug candidates. Therefore, to find novel compounds against COVID-19, we created a library of 412 lichen compounds and subjected to virtual screening against the SARS-CoV-2 Main protease (Mpro). All the ligands were virtually screened, and 27 compounds were found to have high affinity with Mpro. These compounds were assessed for drug-likeness analysis where two compounds were found to fit well for redocking studies. Molecular docking, drug-likeness, X-Score, and toxicity analysis resulting in two lichen compounds, Calycin and Rhizocarpic acid with Mpro-inhibiting activity. These compounds were finally subjected to molecular dynamics simulation to compare the dynamics behavior and stability of the Mpro after ligand binding. The binding energy was calculated by MM-PBSA method to determine the intermolecular protein–ligand interactions. Our results showed that two compounds; Calycin and Rhizocarpic acid had the binding free energy of − 42.42 kJ mol/1 and − 57.85 kJ mol/1 respectively as compared to reference X77 (− 91.78 kJ mol/1). We concluded that Calycin and Rhizocarpic acid show considerable structural and pharmacological properties and they can be used as hit compounds to develop potential antiviral agents against SARS-CoV-2. These lichen compounds may be a suitable candidate for further experimental analysis. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10118-x) contains supplementary material, which is available to authorized users.