Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19
et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979
, Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and.., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979
Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 Mpro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.
Hussein et al., 25 Jan 2021, peer-reviewed, 2 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
Molecular docking identification for the efficacy of some zinc complexes with chloroquine and hydroxychloroquine against main protease of COVID-19
Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979
Vast amount of research has been recently conducted to discover drugs for efficacious treatment of corona virus disease 2019 . 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.
Declaration of Competing Interest I have no conflicts of interest to disclose.
CRediT
References
Ali, Optimizing the use of hydroxychloroquine in the management of COVID-19 given its pharmacological profile, J. Pharm. Res. Int, doi:10.9734/jpri/2020/v32i830468
Andersag, Breitner, Jung, Process for the preparation of quinoline compounds containing amino groups with basic substituents in the 4-position, German Patent
Baildya, Ghosh, Chattopadhyay, Inhibitory activity of hydroxychloroquine on COVID-19 main protease: an insight from MD-simulation studies, J. Mol. Struct, doi:10.1016/j.molstruc.2020.128595
Burikhanov, Chloroquine-inducible par-4 secretion is essential for tumor cell apoptosis and inhibition of metastasis, Cell Rep, doi:10.1016/j.celrep.2016.12.051
Carlucci, Ahuja, Petrilli, Rajagopalan, Jones et al., Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients, medRxiv (2020) (except HIV/AIDS), preprintMay, doi:10.1101/2020.05.02.20080036
Cheke, The molecular docking study of potential drug candidates showing anti-COVID-19 activity by exploring of therapeutic targets of SARS-CoV-2, EJMO, doi:10.14744/ejmo.2020.31503
Cortegiani, Ippolito, Ingoglia, Einav, Chloroquine for COVID-19: rationale, facts, hopes, Crit. Care, doi:10.1186/s13054-020-02932-4
Dayer, Taleb-Gassabi, Dayer, Lopinavir; a potent drug against coronavirus infection: insight from molecular docking study, Arch. Clin. Infect. Dis, doi:10.5812/archcid.13823
Derwand, Scholz, Does zinc supplementation enhance the clinical efficacy of chloroquine/hydroxychloroquine to win today's battle against COVID-19?, Med. Hypotheses, doi:10.1016/j.mehy.2020.109815
Devaux, -M. Rolain, Raoult, ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and COVID-19 disease outcome, J. Microbiol. Immunol. Infect, doi:10.1016/j.jmii.2020.04.015
Evans, Williamson, Chemistry of clinically active anti-inflammatory compounds, in: Chemistry of clinically active anti-inflammatory compounds
Felsenstein, Herbert, Mcnamara, Hedrich, COVID-19: immunology and treatment options, Clin. Immunol, doi:10.1016/j.clim.2020.108448
Geleris, Observational study of hydroxychloroquine in hospitalized patients with COVID-19, N. Engl. J. Med, doi:10.1056/NEJMoa2012410
George, An Introduction to Hydrogen Bonding
Hashem, Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: a narrative review, Travel Med. Infect. Dis, doi:10.1016/j.tmaid.2020.101735
Haładyj, Sikora, Felis-Giemza, Olesi Ńska, Antimalarials-are they effective and safe in rheumatic diseases?, Reumatologia/Rheumatology, doi:10.5114/reum.2018.76904
Humphrey, Dalke, Schulten, VMD: visual molecular dynamics, J. Mol. Graph, doi:10.1016/0263-7855(96)00018-5
Irwin, Automated docking screens: a feasibility study, J. Med. Chem, doi:10.1021/jm9006966
Kearney, Chloroquine as a potential treatment and prevention measure for the 2019 novel coronavirus: a review, Med. Pharmacol, doi:10.20944/preprints202003.0275.v1
Krafts, Hempelmann, Skórska-Stania, From methylene blue to chloroquine: a brief review of the development of an antimalarial therapy, Parasitol. Res, doi:10.1007/s00436-012-2886-x
Lamoureux, Zoubeidi, Dual inhibition of autophagy and the AKT pathway in prostate cancer, Autophagy, doi:10.4161/auto.24921
Lee, CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field, J. Chem. Theory Comput, doi:10.1021/acs.jctc.5b00935
Manning, Structural and some medicinal characteristics of the copper(II)-hydroxychloroquine complex, Bioorg. Med. Chem. Lett
Mengist, Fan, Jin, Designing of improved drugs for COVID-19: crystal structure of SARS-CoV-2 main protease Mpro, Signal Transduct. Target. Ther, doi:10.1038/s41392-020-0178-y
Morris, AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J. Comput. Chem, doi:10.1002/jcc.21256
Navarro, Castro, Madamet, Amalvict, Benoit et al., Metalchloroquine derivatives as possible anti-malarial drugs: evaluation of antimalarial activity and mode of action, Malar. J, doi:10.1186/1475-2875-13-471
Navarro, Goitia, Silva, Velásquez, Ojeda et al., Synthesis and characterization of new copper-and zinc-chloroquine complexes and their activities on respiratory burst of polymorphonuclear leukocytes, J. Inorg. Biochem, doi:10.1016/j.jinorgbio.2005.05.002
Obaleye, Caira, Tella, Synthesis, characterization and crystal structure of a polymeric zinc(II) complex containing the antimalarial quinine as ligand, J. Chem. Crystallogr, doi:10.1007/s10870-007-9236-3
Pantsar, Poso, Binding affinity via docking: fact and fiction, Molecules, doi:10.3390/molecules23081899
Phillips, Braun, Wang, Scalable molecular dynamics with NAMD, J. Comput. Chem, doi:10.1002/jcc.20289
Rainsford, Parke, Clifford-Rashotte, Kean, Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases, Inflammopharmacology, doi:10.1007/s10787-015-0239-y
Shittu, Afolami, Improving the efficacy of chloroquine and hydroxychloroquine against SARS-CoV-2 may require zinc additives -A better synergy for future COVID-19 clinical trials, Le Infezioni in Medicina
Somer, Kallio, Pesonen, Pyykkö, Huupponen et al., Influence of hydroxychloroquine on the bioavailability of oral metoprolol, Br. J. Clin. Pharmacol
Suranagi, Rehan, Goyal, Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence, doi:10.1101/2020.04.16.20068205
Verschooten, Autophagy inhibitor chloroquine enhanced the cell death inducing effect of the flavonoid luteolin in metastatic squamous cell carcinoma cells, PLoS ONE, doi:10.1371/journal.pone.0048264
Zhou, Dai, Tong, COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression, J. Antimicrob. Chemother, doi:10.1093/jac/dkaa114
Śled Ź, Caflisch, Protein structure-based drug design: from docking to molecular dynamics, Curr. Opin. Struct. Biol, doi:10.1016/j.sbi.2017.10.010
Loading..
Please send us corrections, updates, or comments. Vaccines and
treatments are complementary. All practical, effective, and safe means should
be used based on risk/benefit analysis. No treatment, vaccine, or intervention
is 100% available and effective for all current and future variants. We do not
provide medical advice. Before taking any medication, consult a qualified
physician who can provide personalized advice and details of risks and
benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.