Inhibition of multiple SARS-CoV-2 proteins by an antiviral biomolecule, seselin from Aegle marmelos deciphered using molecular docking analysis

Abstract Our earlier experimental and computational report produced the evidence on anti-viral nature of the compound seselin purified from the leaf extracts of Aegle marmelos against Bombyx mori Nuclear Polyhedrosis Virus (BmNPV). In the pandemic situation of COVID-19 caused by SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin has been made to test its efficacy against multiple targets of SARS-COV-2 such as SARS-CoV-2S spike protein, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease. The ligand, seselin showed the best interaction with receptors SARS-CoV-2S protein, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease with a binding energy of -6.6 kcal/mol, -6.9 kcal/mol and -6.7 kcal/mol, respectively. Docking analysis with three different receptors identified that all the computationally predicted lowest energy complexes were stabilized by intermolecular hydrogen bonds and stacking interactions. The aminoacid residues involved in interactions are THR111 and GLN110 for spike protein, SER1003, ALA958 and THR961 for COVID-19 main protease, and for SARS-CoV-2 (2019-nCoV) main protease, it is THR111, GLN110 and THR292. The outcome of pharmacokinetic analysis suggests that the compound had favourable drugability properties by obeying Lipinski rule of five with efficient ADME properties and exhibiting high affinity towards the binding site that it was directed to. The results suggest that the seselin has inhibitory potential over multiple SARS-COV-2 targets and holds a high potential to work effectively as a novel drug for COVID-19, if evaluated in experimental set ups in foreseeable future.