Function of Anti-CoV Structure Using INH [1-6]- Tyr160-Met161-His162 Complex

ABSTRACT

Coronaviruses (CoVs), positive-stranded RNA viruses, can infect humans and multiple species of animals, cause enteric, respiratory, and central nervous system diseases in many species, and are attractive targets for anti-CoV drug design through a pivotal role in viral gene expression and replication through the proteolytic processing of replicase polyproteins. In this work, it has been investigated the junction of six inhibitors including N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide (INH1), NSC 158362 (INH2), JMF 1586 (INH3), (N-(2-aminoethyl)-1-1ziridine-ethanamine) (INH4), [(Z)-1-thiophen-2-ylethylideneamino]thiourea (INH5), and Vanillinbananin (INH6) to coronavirus by forming the complexes of inhibitor-CoV through the hydrogen bonding using the physicochemical properties of the heat of formation, Gibbs free energy, electronic energy, the charge distribution of active parts in the hydrogen bonding, NMR estimation of inhibitor jointed to the database amino acids fragment of Tyr-Met-His as the selective zone of the CoV, positive frequency and intensity of different normal modes of these structures. The theoretical calculations were done at various levels of theory to gain more accurate equilibrium geometrical results. A comparison of these structures with two configurations provides new insights for the design of substrate-based inhibitors targeting CoV. This indicates a feasible model for designing wide-spectrum inhibitors against CoV-associated diseases. The structure-based optimization of these structures has yielded two more efficacious lead compounds, N and O atoms, through forming the hydrogen bonding (H-bonding) with potent inhibition against CoV (Tyr160-Met161-His162), which has been abbreviated as TMH in this work.