Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies

• Published in: Journal of molecular structure 2022-01, Vol.1248, p.131481-131481, Article 131481
• Main Authors: Gholivand, Khodayar, Mohammadpanah, Fahimeh, Pooyan, Mahsa, Roohzadeh, Roohollah
• Format: Article
• Language: English
• Subjects: COVID-19 main protease (Mpro); Docking; Phosphoguanidine; Phosphopyrazine; QSAR
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131481

•Docking interaction of a series of phosphoramides with COVID-19 was studied.•Phosphoramide inhibitors exhibited close interaction with COVID-19.•QSAR, DFT were used to study the inhibition affecting factors of Mpro activity.•Aromaticity is a major contributing factor to the inhibitory effect of compounds. The recent prevalence of coronavirus disease in 2019 (COVID-19) has triggered widespread global health concerns.Antiviral drugs based on phosphoramides have significant inhibitory activity against the main protease (Mpro) of the virus and prevent transcription and viral replication. Hence, in order to design and introduce a group of inhibitors affecting the coronavirus, 35 phosphoramide compounds based on phospho-guanine and phospho-pyrazine derivatives were selected for molecular docking study. The results showed that most phosphoguanides containing the amino benzimidazole have a high interaction tendency with COVID-19. Among them, compound 19 was identified as the strongest inhibitor with the -9.570 kcal/mol binding energy whereas, the binding energy of Remdesivir is -6.75 kcal/mol. The quantitative structure-activity relationship (QSAR) results demonstrated that the number of aromatic rings, amide's nitrogens and their ability in π-staking, and hydrogen interactions with Mpro active sites are major factors contributing to the inhibitory activity of these compounds.Also, the NCI-RDG and DFT results were in good accordance with those of QSAR and molecular docking. The findings of this investigation can be underlying the synthesis of effective and efficient drugs against COVID-19. [Display omitted]