In silico molecular docking: Evaluation of coumarin based derivatives against SARS-CoV-2

The unique anthropological coronavirus which has been titled as SARS-CoV-2 was originally arisen in late 2019 in Wuhan, China affecting respiratory infection named as COVID-19. Coronavirus is disturbing human life in an exceptional method and has converted a public health global crisis. Natural products are ahead consideration due to the huge beneficial window and effective anti-inflammatory, immunomodulatory, antioxidant and antiviral possessions. Consequently, the present study was intended to display inhibition ability of natural products coumarins and their analogues against SARS coronavirus.

The present study, aims to forecast theoretical assembly for the protease of COVID-19 and to discover advance whether this protein may assist as a target for protease inhibitors such as psoralen, bergapten, imperatorin, heraclenin, heraclenol, saxalin, oxepeucedanin, angelicin, toddacoumaquinone, and aesculetin. The docking score of these natural coumarin analogues compared with standard Hydroxychloroquine. Whereas the 3D assembly of main protease of SARS coronavirus was forecast with SWISS MODEL web server, and molecular interaction studies amongst target protein and ligands were done with AutoDock Vina software.

The study more exposed that all the inhibitors acquired with negative dock energy against the target protein. Molecular docking investigation displayed that natural coumarin analogue toddacoumaquinone displayed a remarkable inhibition ability with the binding energy of -7.8 kcal/mol than other compounds against main protease of SARS coronavirus in intricate with α-ketoamide (PDB ID: 5N5O). The synthetic coumarin analogue (1 m) also displayed the comparable inhibition ability with a binding energy of -7.1 kcal/mol against main protease of SARS coronavirus in intricate with α-ketoamide. Keeping the overhead results of ADME and toxicity, all tested compounds were recognized as drug-like nature, passing Lipinski's "Rule of 5" with 0 violation except α-ketoamide passes Lipinski's "Rule of 5" with 1 violation MW > 500. The projected constraints are within the assortment of recognized values.

Based upon the results of the manifold sequence alliance, natural and synthetic coumarin binding sites were preserved. The present in silico examination thus, delivers structural awareness about the protease of COVID-19 and molecular relations with some of the recognised protease inhibitors.