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Journey of Chloroquine/ Hydroxychloroquine in the management of COVID-19


Affiliations
1 Assistant Professor, Deptt. of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Chandigarh, India
2 Professor, Deptt. of Pharmacology, Govt. Medical College and Hospital, Sector 32, Chandigarh, India
3 Assistant Professor, Deptt. of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Chandigarh,, India
4 Deptt. of Critical Care, Max Superspeciality Hospital, Mohali (Punjab),, India
     

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Chloroquine was discovered in 1934 and since then it is used as an antimalarial drug saving millions of lives. Chloroquine and its analogue Hydroxychloroquine possess pleotropic pharmacological actions and are of proven value in multiple conditions ranging from protozoal to autoimmune diseases. Advantage with these drugs is their well-documented tolerability profile. In Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2), these drugs in vitro showed promising results working at multiple sites ranging from prevention of entry of the virus into human cells, halting the multiplication by altering the pH of internal organelles towards basic side and via exocytosis. These drugs also act as immunomodulators to prevent flare up of cytokines and interleukin cascade, thus preventing multiple organ dysfunction syndrome. In this review we trend the journey of these drugs, how high hopes were pinned to their use but they failed to show any mortality benefit in hospitalized patients. However, still certain studies are underway to explore their role in prophylaxis or otherwise. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms like “SARSCoV-2”, “COVID-19”, “Chloroquine” and “Hydroxychloroquine”.

Keywords

SARS-CoV-2, COVID-19, Chloroquine, Hydroxychloroquine.
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  • Colson P, Raoult D. Fighting viruses with antibiotics: an overlooked path. Int J Antimicrob Agents 2016; 48(4):349-52.
  • Suttle CA. Marine viruses—major players in the global ecosystem. Nat Rev Microbiol 2007; 5:801–12.
  • Al-Tawfiq JA, Al-Homoud AH, Memish ZA. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med Infect Dis 2020; 34:101615.
  • Gade A et al, SARS-CoV-2 The beta genome coronavirus: A brief overview, pathogenesis and treatment. Asian J Res Pharm Sci 2020;10(4):299-310.
  • Srivastava A, et al. Socio Economic Impact Of COVID-A Review. Asian J Res Chem 2020; 13(6):497-501.
  • Tade RS et al. Historical Dilemmas of Coronavirus Disease(COVID-19): Public Health Emergency, Management perspectives and Global impacts. Int J of Nursing Education and research 2021;9(3):345-6.
  • Naresh BV. A review of the 2019 Novel Coronavirus (COVID-19) pandemic. Asian J Pharm Res 2020;10(3): 233-38.
  • Yadav AR, Mohite SK. A review on Severe Acute Respiratory Infection (SARI) and its clinical management in suspect/ Confirmed Novel Coronavirus(nCoV) Cases. Res J Pharma Dosage Forms and Tech 2020; 12(3):178-180.
  • Ahmad S, et al. Epidemiology, risks, myths, pharmacotherapeutic management and socio economic burden due to novel COVID-19: A recent update. Research J Pharm and Tech 2020;13(9): 4435-42.
  • Kumar R, et al. A valuable insight to the novel deadly COVID-19: A Review. Res J pharmacology and pharmacodynamics. 2020:12(13):111-16.
  • Lu R,et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395:565-74.
  • Hulswit RJG, de Haan CAM , Bosch BJ. Coronavirus Spike Protein and Tropism Changes. In: Ziebuhr J, editor. Coronaviruses. Advances in virus research. Vol. 96. Science direct 2016. Pp.30-48.
  • Mercorelli B, Palu G, Loregian A. Drug Repurposing for Viral Infectious Diseases: How Far Are We? Trends Microbiol 2018;26(10):865-76.
  • Rokade M, Khandagale P. Coronavirus Disease: A review of a new threat to public health. Asian J Pharm Res 2020;10(3):241-44.
  • Fehr AR, Perlman S. Coronaviruses: An Overview of Their Replication and Pathogenesis. In: Maier H., Bickerton E., Britton P, editors. Coronaviruses. Methods in Molecular Biology, vol 1282, New York: Humana Press; 2015.pp. 1-23.
  • Xu X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020; 63(3):457-60.
  • Shang J, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A 2020; 117(21):11727-734.
  • Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microb Infect 2020; 9(1):601-4.
  • Jain MS, Barhate SD. Corona viruses are a family of viruses that range from the common cold to MERS corona virus: A review. Asian J Res Pharm Sci 2020; 10(3):204-210.
  • Blau DM, Holmes KV. Human coronavirus HCoV-229E enters susceptible cells via the Endocytic pathway. Adv Exp Med Biol 2001; 494:193-98.
  • Groneberg DA, Hilgenfeld R, Zabel P. Molecular mechanisms of severe acute respiratory Syndrome (SARS). Respir Res 2005; 6(1):8-8.
  • Kishor RS, Ramhari BM. Introduction to Covid-19. Research J Science and Tech 2020; 12(4):338-45.
  • Lu H. Drug treatment options for the 2019-new coronavirus (2019- nCoV). Biosci Trends 2020; 14(1):69-71.
  • Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov Today 2020; 25(4):668-88.
  • Li H, et al. Potential antiviral therapeutics for 2019 Novel Coronavirus. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(0):E002.
  • Sharun K, et al. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Hum Vaccin Immunother 2020; 16(6):1232-38.
  • Jones L.H., Bunnage M.E. Applications of chemogenomic library screening in drug discovery. Nat. Rev. Drug Discov 2017; 16:285– 96.
  • Strittmatter S.M. Overcoming drug development bottlenecks with repurposing: old drugs learn new tricks. Nat. Med 2014; 20:590– 91.
  • Plantone D, Koudriavtseva T. Current and Future Use of Chloroquine and Hydroxychloroquine in Infectious, Immune, Neoplastic, and Neurological Diseases: A Mini-Review. Clin Drug Investig 2018; 38(8):653-71.
  • Pillaiyar T, Meenakshisundaram S, Manickam M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov Today 2020; 25(4):668-88.
  • Dyall J, et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 2014;58(8):4885-93.
  • de Wilde AH, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 2014; 58(8):4875-84.
  • Chan JF, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect 2013; 67(6):606- 16.
  • Packard RM. The origins of antimalarial-drug resistance. N Engl J Med 2014; 371(5):397-99.
  • Arrow KJ, Panosian C, Gelband H, editors. Institute of Medicine (US) Committee on the Economics of Antimalarial Drugs. Saving Lives, Buying Time: Economics of Malaria Drugs in an Age of Resistance. Washington (DC): National Academies Press (US); 2004.
  • Wolf R, Wolf D, Ruocco V. Antimalarials: unapproved uses or indications. Clin Dermatol 2000; 18: 17–35.
  • Shukla AM, Wagle Shukla A. Expanding horizons for clinical applications of chloroquine, hydroxychloroquine, and related structural analogues. Drugs Context 2019; 8:2019-9-1.
  • Schrezenmeier E, Dorner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 2020;16(3):155-66.
  • McLachlan AJ, et al. Bioavailability of hydroxychloroquine tablets in patients with rheumatoid arthritis. Br J Rheumatol 1994; 33(3):235–39.
  • Al-Bari MA. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J Antimicrob Chemother 2015; 70(6):1608-21.
  • Rainsford KD, et al. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology2015; 23(5):231-69.
  • Carmichael SJ, Charles B, Tett SE. Population pharmacokinetics of hydroxychloroquine in patients with rheumatoid arthritis. Ther Drug Monit 2003; 25(6):671-81.
  • Collins KP, Jackson KM, Gustafson DL. Hydroxychloroquine: A Physiologically-Based Pharmacokinetic Model in the Context of Cancer-Related Autophagy Modulation. J Pharmacol Exp Ther 2018; 365(3):447-59.
  • Munster T, et al. Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Arthritis Rheum 2002; 46(6):1460-69.
  • Costedoat-Chalumeau N, et al. A Critical Review of the Effects of Hydroxychloroquine and Chloroquine on the Eye. Clin Rev AllergyImmunol 2015; 49(3):317-326.
  • Moore BR, et al. Pharmacokinetics, pharmacodynamics, and allometric scaling of chloroquine in a murine malaria model. Antimicrob Agents Chemother 2011; 55(8):3899-907.
  • Gonzalez-Hernandez I, et al. Distribution of hydroxychloroquine in lymphoid tissue in a rabbit model for HIV infection. Antimicrob Agents Chemother 2014; 58(1):584-86.
  • Martin RE, et al. Chloroquine transport via the malaria parasite's chloroquine resistance transporter. Science 2009; 325(5948):1680- 82.
  • Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents 2007; 30(4):297-308.
  • Kaufmann AM, Krise JP. Lysosomal sequestration of aminecontaining drugs: analysis and therapeutic implications. J Pharm Sci 2007; 96: 729–46.
  • Wallace DJ, et al. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol 2012; 8:522-33.
  • Sieczkarski SB, Whittaker GR. Dissecting virus entry via endocytosis. J Gen Virol 2002; 83:1535–45.
  • Blau D, Holmes K. Human Coronavirus HCoV-229E enters susceptible cells via the endocytic pathway. In: Lavi E, editor. The Nidoviruses, Coronaviruses and Arteriviruses. New York: Kluwer; 2001. pp 193–97.
  • Ferreira DF, et al.Weak bases affect late stages of Mayaro virus replication cycle in vertebrate cells. J Med Microbiol 2000; 49: 313–18.
  • Harley CA, Dasgupta A, Wilson DW. Characterization of herpes simplex virus-containing organelles by subcellular fractionation: role for organelle acidification in assembly of infectious particles. J Virol 2001; 75: 1236–51.
  • Savarino A, et al. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis 2003 Nov; 3(11):722-7.
  • Kwiek JJ, Haystead TA, Rudolph J. Kinetic mechanism of quinine oxidoreductase 2 and its inhibition by the antimalarial quinolines. Biochemistry 2004; 43:4538–47.
  • Vincent MJ, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread.Virol J 2005;2:69.
  • Keyaerts E, et al. In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine. Biochem Biophys Res Commun. 2004;323(1):264-8.
  • Vincent MJ, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2:69.
  • De Wilde AH, et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother. 2014; 58(8):4875-84.
  • Dyall J, et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 2014; 58(8):4885-93.
  • Yao X, et al. In vitroantiviral activity and projection of optimized dosing design ofhydroxychloroquine for the treatment of severe acute respiratorysyndrome coronavirus 2 (SARS‑CoV‑2). Clin Infect Dis 2020; 71(15):732-39.
  • Wang M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3):269-71.
  • Liu J, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 2020; 6:16.
  • 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 2020;14(1):72-73.
  • Gautret P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020;56(1):105949.
  • Purwati, et al. A Randomized, Double-Blind, Multicenter Clinical Study Comparing the Efficacy and Safety of a Drug Combination of Lopinavir/Ritonavir-Azithromycin, Lopinavir/RitonavirDoxycycline, and Azithromycin-Hydroxychloroquine for Patients Diagnosed with Mild to Moderate COVID-19 Infections. Biochem Res Int 2021 ;2021:6685921.
  • Chowdhury MS, Rathod J, Gernsheimer J. A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19. Acad Emerg Med 2020 ;27(6):493-504.
  • Tang W, et al. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. Available from:https://www.medrxiv.org/content/10.1101/2020.04.10.20060 558v1.
  • Borba MGS, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) Infection: A Randomized Clinical Trial. JAMA Netw Open 2020; 3(4):e208857.
  • Fihn SD, Perencevich E, Bradley SM. Caution Needed on the Use of Chloroquine and Hydroxychloroquine for Coronavirus Disease 2019. JAMA Netw Open 2020; 3(4):e209035.
  • Mercuro NJ, et al. Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. 2020;5(9):1036-41.
  • Bessiere F,et al. Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit. JAMA Cardiol 2020; 5(9):1067–69.
  • Magagnoli J, et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. Med 2020;1(1):114-127.
  • Recovery Collaborative Group, Horby P,et al. Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19. N Engl J Med 2020;383(21):2030-40.
  • Lacout A, et al. Hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2021;384(9):881-2.
  • Manivannan E, et al. The Rise and Fall of Chloroquine/Hydroxychloroquine as Compassionate Therapy of COVID-19. Front Pharmacol 2021;12:584940.
  • Axfors C, et al. Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials. Nat Commun. 2021;12(1):2349.
  • Rahimi H, et al. Effect of hydroxychloroquine on COVID-19 prevention in cancer patients undergoing treatment: study protocol for a randomized controlled trial. Trials. 2021;22(1):349.
  • Hydroxychloroquine for Treatment of Non-Severe COVID-19 (HONEST) Available from:https://clinicaltrials.gov/ct2/show/NCT04860284.[Last accessed on 2021 Aug 6].
  • Efficacy of Pre-exposure Treatment with Hydroxy-Chloroquine on the Risk and Severity of COVID-19 Infection (PREPCOV). Available from https://clinicaltrials.gov/ct2/show/NCT04481633. [Last accessed on 2021 Aug 6]

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  • Journey of Chloroquine/ Hydroxychloroquine in the management of COVID-19

Abstract Views: 110  |  PDF Views: 0

Authors

Kavita Sekhri
Assistant Professor, Deptt. of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Chandigarh, India
Sangeeta Bhanwra
Professor, Deptt. of Pharmacology, Govt. Medical College and Hospital, Sector 32, Chandigarh, India
Ruchika Nandha
Assistant Professor, Deptt. of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Chandigarh,, India
Suruchi Aditya
Assistant Professor, Deptt. of Pharmacology, Dr Harvansh Singh Judge Institute of Dental Sciences, Panjab University, Chandigarh,, India
Deepak Bhasin
Deptt. of Critical Care, Max Superspeciality Hospital, Mohali (Punjab),, India

Abstract


Chloroquine was discovered in 1934 and since then it is used as an antimalarial drug saving millions of lives. Chloroquine and its analogue Hydroxychloroquine possess pleotropic pharmacological actions and are of proven value in multiple conditions ranging from protozoal to autoimmune diseases. Advantage with these drugs is their well-documented tolerability profile. In Severe Acute Respiratory Syndrome Corona virus-2 (SARS-CoV-2), these drugs in vitro showed promising results working at multiple sites ranging from prevention of entry of the virus into human cells, halting the multiplication by altering the pH of internal organelles towards basic side and via exocytosis. These drugs also act as immunomodulators to prevent flare up of cytokines and interleukin cascade, thus preventing multiple organ dysfunction syndrome. In this review we trend the journey of these drugs, how high hopes were pinned to their use but they failed to show any mortality benefit in hospitalized patients. However, still certain studies are underway to explore their role in prophylaxis or otherwise. Medline, Medscape, EMBASE, Cochrane database, Scopus and clinicaltrials.gov were searched using terms like “SARSCoV-2”, “COVID-19”, “Chloroquine” and “Hydroxychloroquine”.

Keywords


SARS-CoV-2, COVID-19, Chloroquine, Hydroxychloroquine.

References