CLOROQUINA – Desde 2003, 50 estudos comprovam eficácia de cloroquina

CLOROQUINA

Desde 2003, 50 estudos comprovam eficácia de cloroquina

Bernardo Küster
16 de Maio de 2020 às 16:11
Conheça 50 estudos que comprovam, desde 2003, a eficácia da cloroquina e da hidroxicloroquina..

Ontem (15), durante um debate na rede CNN sobre eficácia da (hidroxi)cloroquina, Dr Paolo Zanotto, virologista da USP, prometeu ao seu oponente, o infectologista Marcos Boulos, uma lista de 35 referências que comprovariam sua tese, favorável ao uso precoce do medicacmento. Bem, este jornal acaba de receber de Zanotto não 35, mas 50 estudos nessa linha. A “listinha” contém referências sobre as 4-AQs, suas atividades e seu uso antiviral e na COVID-19 desde 2003.

Na mensagem, Zanotto alertou: “Agora os inteligentinhos vão ter que estudar”. E vão mesmo. Deve-se parar com essa história de que “não há estudos” sobre a eficácia do medicamento, ou que seus efeitos colaterais seriam tão malignos que seu uso seria inoportuno. Os documentos abaixo, compilados por Paolo Zanotto, mostram o poder antiviral da (hidroxi)cloroquina, desde 2003, quando ocorreu a epidemia de H1N1. A maioria dos estudos aqui apresentados (do 18 ao 50) são estudos deste ano relacionados ao vírus SARS-CoV-2, causador da doença Covid-19.

1 Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis 2003; 3: 722–27.

2 Joshi SR, Butala N, Patwardhan MR, Daver NG, Kelkar D. Low cost anti- retroviral options: chloroquine based ARV regimen combined with hydroxyurea and lamivudine: a new economical triple therapy.
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3 Lori F, Foli A, Groff A, et al. Optimal suppression of HIV replication by low- dose hydroxyurea through the combination of antiviral and cytostatic (‘virostatic’) mechanisms. AIDS 2005; 19: 1173–81. 


4 Paton NI, Aboulhab J. Hydroxychloroquine, hydroxyurea and didanosine as initial therapy for HIV-infected patients with low viral load: safety, efficacy and resistance profile after 144 weeks. HIV Med 2005; 6: 13–20. 


5 Luchters SMF, Veldhuijzen NJ, Nsanzabera D, et al. A phase I/II randomised placebo controlled study to evaluate chloroquine administration to reduce HIV-1 RNA in breast milk in an HIV-1 infected breastfeeding population: the CHARGE Study. XV International Conference on AIDS; Bangkok, Thailand; July 11–16, 2004. Abstract TuPeB4499. 


6 Savarino A, Lucia MB, Rastrelli E, et al. Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with protease inhibitors. J Acquir Immune Defic Syndr 1996; 35: 223–32.

7 Keyaerts E, Vijgen L, Maes P, Neyts J, Van Ranst M. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun 2004; 323: 264–68.

8 Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69.

9 Miller DK, Lenard J. Antihistaminics, local anesthetics, and other amines as antiviral agents. Proc Natl Acad Sci USA 1981; 78: 3605–09.

10 Shibata M, Aoki H, Tsurumi T, et al. Mechanism of uncoating of influenza B virus in MDCK cells: action of chloroquine. J Gen Virol 1983; 64: 1149–56.

11 Donatelli I, Campitelli L, Di Trani L, et al. Characterization of H5N2 influenza viruses from Italian poultry. J Gen Virol 2001; 82: 623–30.

12 Jones G, Willett P, Glen RC, Leach AR, Taylor R. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997; 267: 727–48.

13 Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinone oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry 2004; 43: 4538–47.

14 National Center for Biotechnology Information. MMDB—Entrez’s Structure Database. http://www.ncbi.nlm.nih.gov/Structure/MMDB/ mmdb.shtml (accessed Dec 14, 2005).

15 Olofsson S, Kumlin U, Dimock K, Arnberg N. Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infect Dis 2005; 5: 184–88.

16 Savarino A, Di Trani L, Donatelli I, Cauda R, Cassone A. New insights into the antiviral effects of chloroquine. The Lancet Infectious Diseases Vol. 6 February 2006.

  1. Browning D.J. Pharmacology of Chloroquine 2 and Hydroxychloroquine. Chapter 2 in D.J. Browning, Hydroxychloroquine and Chloroquine Retinopathy, 35 DOI 10.1007/978-1-4939-0597-3_2, © Springer Science+Business Media New York 2014.
  2. Yao et al., 2020. 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). https://www.ncbi.nlm.nih.gov/pubmed/32150618
  3. Colson et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. International Journal of Antimicrobial Agents. Journal homepage: https://www.journals.elsevier.com/international-journal-of-antimicrobial-agents https://www.sciencedirect.com/science/article/pii/S0924857920300820?via%3Dihub
  4. Wang, M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30, 269–271 (2020).
  5. Gao, J., Tian, Z. & Yang, X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends 14, 72–73 (2020).
  6. Gordon et al. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing bioRxiv preprint doi: https://www.biorxiv.org/content/10.1101/2020.03.22.002386v3
  7. Van Thuan Hoang, Valérie Giordanengo,Vera Esteves Vieira, Hervé Tissot Dupont, Philippe Colson , Eric Chabriere, Bernard La Scola, Jean-Marc Rolain,Didier Raoult , Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents (2020), https://www.sciencedirect.com/science/article/pii/S0924857920300996?via%3Dihub
  8. Chen et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3
  9. Elisabeth Mahase. Covid-19: what treatments are being investigated? BMJ 2020;368:m1252 doi: 10.1136/bmj.m1252 (Published 26 March 2020).
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  11. Sahraei, Z., Shabani, M., Shokouhi, S. and Saffaei, A., 2020. Aminoquinolines Against Coronavirus Disease 2019 (COVID-19): Chloroquine or Hydroxychloroquine. International Journal of Antimicrobial Agents, p.105945.
  12. Chauhan, A. and Tikoo, A., 2015. The enigma of the clandestine association between chloroquine and HIV‐1 infection. HIV medicine, 16(10), pp.585-590.
  13. Keyaerts, E., Li, S., Vijgen, L., Rysman, E., Verbeeck, J., Van Ranst, M. and Maes, P., 2009. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrobial agents and chemotherapy, 53(8), pp.3416-3421.
  14. Vincent, M.J., Bergeron, E., Benjannet, S., Erickson, B.R., Rollin, P.E., Ksiazek, T.G., Seidah, N.G. and Nichol, S.T., 2005. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology journal, 2(1), p.69.

31 Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H., Li, Y., Hu, Z., Zhong, W. and Wang, M., 2020. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery, 6(1), pp.1-4.

  1. Savarino, A., Boelaert, J.R., Cassone, A., Majori, G. and Cauda, R., 2003. Effects of chloroquine on viral infections: an old drug against today’s diseases. The Lancet infectious diseases, 3(11), pp.722-727.
  2. Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Niu, P., Liu, X., Zhao, L., Dong, E., Song, C. and Zhan, S., 2020. 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). Clinical Infectious Disease.
  3. Gautret, P., Lagier, J.C., Parola, P., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V.E., Dupont, H.T. and Honoré, S., 2020. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents, p.105949.
  4. Christian A. Devaux, Jean-Marc Rolain, Philippe Colson, Didier Raoult. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, International Journal of Antimicrobial Agents (2020), https://doi.org/10.1016/j.ijantimicag.2020.105938
  5. Singh AK, Singh A, Shaikh A, Singh R, Misra A, Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries, Diabetes & Metabolic Syndrome: Clinical Research & Reviews (2020), doi: https://doi.org/10.1016/j.dsx.2020.03.011
  6. Kaapor KM & Kaapor A. Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review. medRxiv preprint doi: https://doi.org/10.1101/2020.03.24.20042366
  7. Gao J , Tian Z , and Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020. https://doi.org/10.5582/bst.2020.01047
  8. Liu W & Li H. COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism. https://bit.ly/3bx7RxS
  9. Cortegiani et al., A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19, Journal of Critical Care, https://www.sciencedirect.com/science/article/pii/S0883944120303907?via%3Dihub
  10. James M. Sanders, PhD, PharmD; Marguerite L. Monogue, PharmD; Tomasz Z. Jodlowski, PharmD; James B. Cutrell, MD. Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19) A Review JAMA. doi:10.1001/jama.2020.6019 Published online April 13, 2020.
  11. Riou B, Barriot P, Rimailho, A., Baud FJ. Treatment of Severe Cholroquine Poisoning. The New England Journal of Medicine, Vol. 318, Number 1, January 7, 1988. pp. 1-6.
  12. Huang et al. Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.04.26.20081059v1
  13. Membrillo et al. Early hydroxychloroquine is associated with an increase of survival in COVID-19 patients: an observational study. https://www.preprints.org/manuscript/202005.0057/v2
  14. Davido et al. on behalf of the COVID-19 RPC Team Hydroxychloroquine plus azithromycin: a potential interest in reducing in- hospital morbidity due to COVID-19 pneumonia (HI-ZY-COVID)? medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.05.05.20088757v1
  15. Czuppon et al. Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the targeted mechanism. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.05.07.20092965v1
  16. Million, et al., Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France. Travel Medicine and Infectious Disease, https://bit.ly/2LBqc26
  17. Calucci et al. Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.05.02.20080036v1
  18. Tang et al. Hydroxychloroquine in patients mainly with mild to moderate COVID–19: an open–label, randomized, controlled trial. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.04.10.20060558v2
  19. Yu et al. Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19. medRxiv preprint doi: https://www.medrxiv.org/content/10.1101/2020.04.27.20073379v1

Compilação por Paolo Zanotto, D. Phil., em 16 de Maio de 2020.

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