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

Abstract

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 (M pro ) 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 M pro 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.

Synthesis, characterized, QSAR studies and molecular docking of some phosphonates as COVID-19 inhibitors

“…The analysis of Frontier molecular orbitals of ligands is one of the methods used to predict reactive electrophilic or nucleophilic sites [ 44 ]. The lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) are called frontier molecular orbitals.…”

3D‐QSAR, Molecular Docking and Molecular Dynamics Analysis of 1,2,3,4‐Tetrahydroquinoxalines as BRD4/BD2 Inhibitors

“…Therefore, the interactions between drug molecules and receptors are similar to most organic chemical reactions, and their reactivity and reaction sites can be predicted and explained by the electrophilic/nucleophilic properties of the molecules, and global reactivity such as ionization potential (IP), electron nucleophilic potential (EA), electronegativity (χ), overall hardness (η), chemical potential (μ), overall electrophilic index (ω), and overall softness (S) are proposed descriptors. These descriptors can be calculated by the following equations [26] . …”

Experimental and theoretical study of novel amino‐functionalized P(V) coordination compounds suggested as inhibitor of MProof SARS‐COV‐2 by molecular docking study

“…[16][17][18] Recently, the anticoronavirus activity of some phosphoramides has been evaluated. [19] For this purpose, different strategies have been developed among which computational methods such as the molecular docking method are the fastest way to screen candidate drugs on their ligand-protein interactions. [20][21][22] For metal-ligand coordination compounds of PhP(O) [NH- 3,4 Py] 2 ligands (L 3,4 ) with both 3-and 4-pyridinyl substitutions, a Cambridge Structural Database (CSD, version 5.40, with February 2019 update) [23] query gives 20 structures (18 for L 3 and 2 for L 4 ).…”

“…[ 16–18 ] Recently, the anti‐coronavirus activity of some phosphoramides has been evaluated. [ 19 ] For this purpose, different strategies have been developed among which computational methods such as the molecular docking method are the fastest way to screen candidate drugs on their ligand‐protein interactions. [ 20–22 ]…”