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Molecular Docking Identification for the efficacy of Some Zinc Complexes with Chloroquine and Hydroxychloroquine against Main Protease of COVID-19

Hussein et al., Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129979

Jan 2021

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HCQ for COVID-19

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Molecular dynamics analysis recommending Zn (CQ) Cl2(H2O) and Zn (HCQ) Cl2(H2O) as potential inhibitors for COVID-19 M^pro. Zn (HCQ) Cl2(H2O) exhibited a strong binding to the main protease receptor, forming eight hydrogen bonds.

30 preclinical studies support the efficacy of HCQ for COVID-19:

8 In Silico studies Alkafaas, Baildya, González-Paz, Hussein, Navya, Noureddine, Tarek, Yadav

20 In Vitro studies Alsmadi, Andreani, Clementi, Dang, Delandre, Faísca, González-Paz, Kamga Kapchoup, Liu, Milan Bonotto, Mohd Abd Razak, Ou, Purwati, Shang, Sheaff, Wang, Wang (B), Wen, Yao, Yuan

2 In Vivo animal studies Shu-Han Lin, Wen

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1. Alkafaas et al., A study on the effect of natural products against the transmission of B.1.1.529 Omicron, Virology Journal, doi:10.1186/s12985-023-02160-6.biomedcentral.com, doi.org.

2. Alsmadi et al., The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel, AAPS PharmSciTech, doi:10.1208/s12249-023-02627-3.springer.com, doi.org.

3. Andreani et al., In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect, Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228.sciencedirect.com, doi.org.

4. Baildya et al., Inhibitory capacity of Chloroquine against SARS-COV-2 by effective binding with Angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies, Journal of Molecular Structure, doi:10.1016/j.molstruc.2021.129891.sciencedirect.com, doi.org.

5. Clementi et al., Combined Prophylactic and Therapeutic Use Maximizes Hydroxychloroquine Anti-SARS-CoV-2 Effects in vitro, Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704.frontiersin.org, doi.org.

6. Dang et al., Structural basis of anti-SARS-CoV-2 activity of hydroxychloroquine: specific binding to NTD/CTD and disruption of LLPS of N protein, bioRxiv, doi:10.1101/2021.03.16.435741.biorxiv.org, doi.org.

7. Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, doi:10.3390/ph15040445.mdpi.com, doi.org.

8. Faísca et al., Enhanced In Vitro Antiviral Activity of Hydroxychloroquine Ionic Liquids against SARS-CoV-2, Pharmaceutics, doi:10.3390/pharmaceutics14040877.mdpi.com, doi.org.

9. González-Paz et al., Biophysical Analysis of Potential Inhibitors of SARS-CoV-2 Cell Recognition and Their Effect on Viral Dynamics in Different Cell Types: A Computational Prediction from In Vitro Experimental Data, ACS Omega, doi:10.1021/acsomega.3c06968.acs.org, doi.org.

10. Hussein et al., 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.sciencedirect.com, doi.org.

11. Kamga Kapchoup et al., In vitro effect of hydroxychloroquine on pluripotent stem cells and their cardiomyocytes derivatives, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1128382.frontiersin.org, doi.org.

12. Liu et al., Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0.nature.com, doi.org.

13. Milan Bonotto et al., Cathepsin inhibitors nitroxoline and its derivatives inhibit SARS-CoV-2 infection, Antiviral Research, doi:10.1016/j.antiviral.2023.105655.sciencedirect.com, doi.org.

14. Mohd Abd Razak et al., In Vitro Anti-SARS-CoV-2 Activities of Curcumin and Selected Phenolic Compounds, Natural Product Communications, doi:10.1177/1934578X231188861.sagepub.com, doi.org.

15. Navya et al., A computational study on hydroxychloroquine binding to target proteins related to SARS-COV-2 infection, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2021.100714.sciencedirect.com, doi.org.

16. Noureddine et al., Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: molecular docking and DFT calculations, Journal of King Saud University - Science, doi:10.1016/j.jksus.2020.101334.sciencedirect.com, doi.org.

17. Ou et al., Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2, PLOS Pathogens, doi:10.1371/journal.ppat.1009212.plos.org, doi.org.

18. Purwati et al., An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia, PLOS One, doi:10.1371/journal.pone.0252302.plos.org, doi.org.

19. Shang et al., Inhibitors of endosomal acidification suppress SARS-CoV-2 replication and relieve viral pneumonia in hACE2 transgenic mice, Virology Journal, doi:10.1186/s12985-021-01515-1.biomedcentral.com, doi.org.

20. Sheaff, R., A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Chloroquine Activity, bioRxiv, doi:10.1101/2020.08.02.232892.biorxiv.org, doi.org.

21. Shu-Han Lin et al., Inhalable Chitosan-Based Hydrogel as a Mucosal Adjuvant for Hydroxychloroquine in the Treatment for SARS-CoV-2 Infection in a Hamster Model, Journal of Microbiology, Immunology and Infection, doi:10.1016/j.jmii.2023.08.001.sciencedirect.com, doi.org.

22. Tarek et al., Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention, European Journal of Drug Metabolism and Pharmacokinetics, doi:10.1007/s13318-020-00640-6.springer.com, doi.org.

23. Wang et al., Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus, Phytomedicine, doi:10.1016/j.phymed.2020.153333.nih.gov, doi.org.

24. Wang (B) et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0.nature.com, doi.org.

25. Wen et al., Cholinergic α7 nAChR signaling suppresses SARS-CoV-2 infection and inflammation in lung epithelial cells, Journal of Molecular Cell Biology, doi:10.1093/jmcb/mjad048.oup.com, doi.org.

26. Yadav et al., Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study, Research Square, doi:10.21203/rs.3.rs-628277/v1.researchsquare.com, doi.org.

27. Yao et al., In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237.oup.com, doi.org.

28. Yuan et al., Hydroxychloroquine blocks SARS-CoV-2 entry into the endocytic pathway in mammalian cell culture, Communications Biology, doi:10.1038/s42003-022-03841-8.nature.com, doi.org.

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.

This Paper HCQ All

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

R K Hussein, H M Elkhair

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

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