Molecular Docking of Secondary Metabolites from Lichens Targeting Sars-CoV-2 Main Protease (Mpro) and Spike Protein Receptors

This chapter aimed to screen the lichen substances to identify the potential drug to inhibit SARS-CoV-2 main protease and spike protein by molecular docking method.

COVID-19 (Coronavirus disease) is caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2. It is a deadly pathogenic and transmissible virus. Since there is no specific antiviral treatment against COVID-19, identifying new therapeutics is a crucial need. Plant natural substances represent the rich source of active molecules that can find many applications in the field of biology, pharmacy, and medicine including oncology. The COVID-19 main protease (Mpro) and spike proteins (S protein) were selected as target proteins. A total of 108 lichen compounds were subjected to ADMET analysis and 14 compounds were selected based on the ADMET properties and Lipinski’s rule of five. The Schrodinger Glide module software was used to perform molecular docking for screening of chosen individual lichen metabolites against the primary protease and spike protein receptors of SARS-CoV-2. Molecular docking studies of lichen secondary metabolites (14 compounds) were carried out with SARS-CoV-2 proteins. The interactions of lichen metabolites with main protease and spike protein of SARS-CoV-2 tabulated with G-Score, number of hydrogen bonds, bond length, and the interacting residues. Among the lead compounds, fallacinol (1,8-dihydroxy-3-(hydroxymethyl)-6 methoxyanthracene - 9,10-dione) showed the highest binding energy value of -11.83 kcal/mol against spike protein, and 4-O-Demethyl barbatic acid (4-(2,4-dihydroxy-3,6-dimethylbenzoyl)oxy-2-hydroxy-3,6-dimethylbenzoic acid ) exhibited the highest dock score of -11.67 kcal/mol against main protease. This study finding suggests that lichen substances may potential inhibitors of receptors of SARS-CoV-2.