ABSTRACT
MERS-CoV belongs to the coronavirus group. Recent years have seen a rash of coronavirus epidemics. In June 2012, MERS-CoV was discovered in the Kingdom of Saudi Arabia, with 2,591 MERSA cases confirmed by lab tests by the end of August 2022 and 894 deaths at a case-fatality ratio (CFR) of 34.5% documented worldwide. Saudi Arabia reported the majority of these cases, with 2,184 cases and 813 deaths (CFR: 37.2%), necessitating a thorough understanding of the molecular machinery of MERS-CoV. To develop antiviral medicines, illustrative investigation of the protein in coronavirus subunits are required to increase our understanding of the subject. In this study, recombinant expression and purification of MERS-CoV (PLpro), a primary goal for the development of 22 new inhibitors, were completed using a high throughput screening methodology that employed fragment-based libraries in conjunction with structure-based virtual screening. Compounds 2, 7, and 20, showed significant biological activity. Moreover, a docking analysis revealed that the three compounds had favorable binding mood and binding free energy. Molecular dynamic simulation demonstrated the stability of compound 2 (2-((Benzimidazol-2-yl) thio)-1-arylethan-1-ones) the strongest inhibitory activity against the PLpro enzyme. In addition, disubstitutions at the meta and para locations are the only substitutions that may boost the inhibitory action against PLpro. Compound 2 was chosen as a MERS-CoV PLpro inhibitor after passing absorption, distribution, metabolism, and excretion studies; however, further investigations are required.
ABSTRACT
The novel coronavirus 2019 is spreading around the world and causing serious concern. However, there is limited information about novel coronavirus that hinders the design of effective drug. Bioactive compounds are rich source of chemo preventive ingredients. In our present research focuses on identifying and recognizing bioactive chemicals in Lantana camara, by evaluating their potential toward new coronaviruses and confirming the findings using molecular docking, ADMET, network analysis and dynamics investigations.. The spike protein receptor binding domain were docked with 25 identified compounds and 2,4-Ditertbutyl-phenol (-6.3kcal/mol) shows highest docking score, its interactions enhances the increase in binding and helps to identify the biological activity. The ADME/toxicity result shows that all the tested compounds can serve as inhibitors of the enzymes CYP1A2 and CYP2D6. In addition, Molecular dynamics simulations studies with reference inhibitors were carried out to test the stability. This study identifies the possible active molecules against the receptor binding domain of spike protein, which can be further exploited for the treatment of novel coronavirus 2019. The results of the toxicity risk for phytocompounds and their active derivatives showed a moderate to good drug score.
ABSTRACT
An innovative charge-transfer complex between the Schiff base 2-((2-hydroxybenzylidene) amino)-2-(hydroxymethyl) propane-1,3-diol [SAL-THAM] and the π-acceptor, chloranilic acid (CLA) within the mole ratio (1:1) was synthesized and characterized aiming to investigate its electronic transition spectra in acetonitrile (ACN), methanol (MeOH) and ethanol (EtOH) solutions. Applying Job`s method in the three solvents supported the 1:1 (CLA: SAL-THAM) mole ratio complex formation. The formation of stable CT- complex was shown by the highest values of charge-transfer complex formation constants, KCT, calculated using minimum-maximum absorbance method, with the sequence, acetonitrile > ethanol > methanol DFT study on the synthesized CT complex was applied based on the B3LYP method to evaluate the optimized structure and extract geometrical and reactivity parameters. Based on TD-DFT theory, the electronic properties, 1H and 13C NMR, IR, and UV-Vis spectra of the studied system in different solvents showing good agreement with the experimental studies. MEP map described the possibility of hydrogen bonding and charge transfer in the studied system. Finally, a computational approach for screening the antiviral activity of CT - complex towards SARS-CoV-2 coronavirus protease via molecular docking simulation was conducted and confirmed with molecular dynamic (MD) simulation.