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Molecular docking identification for the efficacy of some zinc complexes with chloroquine and hydroxychloroquine against main protease of COVID-19.

ABSTRACT: Vast amount of research has been recently conducted to discover drugs for efficacious treatment of corona virus disease 2019 (COVID-19). The ambiguity about using Chloroquine/ Hydroxychloroquine to treat this illness was a springboard towards new methods for improving the adequacy of these drugs. The effective treatment of COVID-19 using Zinc complexes as add-on to Chloroquine/ Hydroxychloroquine has received major attention in this context. The current studies have shed a light on molecular docking and molecular dynamics methodologies as powerful techniques in establishing therapeutic strategies to combat COVID-19 pandemic. We are proposing some zinc compounds coordination to Chloroquine/ Hydroxychloroquine in order to enhance their activity. The molecular docking calculations showed that Zn(QC)Cl2(H2O) has the least binding energy -7.70 Kcal /mol then Zn(HQC)Cl2(H2O) -7.54 Kcal /mol. The recorded hydrogen bonds were recognized in the strongest range of H Bond category distances. Identification of binding site interactions revealed that the interaction of Zn(QC)Cl2(H2O)with the protease of COVID-19 results in three hydrogen bonds, while Zn(HQC)Cl2(H2O) exhibited a strong binding to the main protease receptor by forming eight hydrogen bonds. The dynamic behavior of the proposed complexes was revealed by molecular dynamics simulations. The outcomes obtained from Molecular dynamics calculations approved the stability of Mpro-Zn(CQ/HCQ)Cl2H2O systems. These findings recommend Zn (CQ) Cl2H2O and Zn (HCQ) Cl2H2O as potential inhibitors for COVID-19 Mpro.

SUBMITTER: Hussein RK

PROVIDER: S-EPMC7830318 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The recent coronavirus outbreak has changed the world's economy and health sectors due to the high mortality and transmission rates. Because the development of new effective vaccines or treatments against the virus can take time, an urgent need exists for the rapid development and design of new drug candidates to combat this pathogen. Here, we obtained antiviral peptides obtained from the data repository of antimicrobial peptides (DRAMP) and screened their predicted tertiary structures for the ability to inhibit the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using multiple combinatorial docking programs, including PatchDock, FireDock, and ClusPro. The four best peptides, DRAMP00877, DRAMP02333, DRAMP02669, and DRAMP03804, had binding energies of -1125.3, -1084.5, -1005.2, and -924.2 Kcal/mol, respectively, as determined using ClusPro, and binding energies of -55.37, -50.96, -49.25, -54.81 Kcal/mol, respectively, as determined using FireDock, which were better binding energy values than observed for other peptide molecules. These peptides were found to bind with the active cavity of the SARS-CoV-2 main protease; at Glu166, Cys145, Asn142, Phe140, and Met165, in addition to the substrate-binding sites, Domain 2 and Domain 3, whereas fewer interactions were observed with Domain 1. The docking studies were further confirmed by a molecular dynamics simulation study, in which several descriptors, including the root-mean-square difference (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), radius of gyration (Rg), and hydrogen bond formation, confirmed the stable nature of the peptide-main protease complexes. Toxicity and allergenicity studies confirmed the non-allergenic nature of the peptides. This present study suggests that these identified antiviral peptide molecules might inhibit the main protease of SARS-CoV-2, although further wet-lab experiments remain necessary to verify these findings.

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Molecular docking identification for the efficacy of some zinc complexes with chloroquine and hydroxychloroquine against main protease of COVID-19.

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