Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Review Article

Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19)

Author(s): Evellyn Claudia Wietzikoski Lovato, Lorena Neris Barboza, Samantha Wietzikoski, Amanda Nascimento Vasques de Souza, Pablo Alvarez Auth, Arquimedes Gasparotto Junior and Francislaine Aparecida dos Reis Lívero*

Volume 27, Issue 1, 2021

Published on: 07 July, 2020

Page: [115 - 126] Pages: 12

DOI: 10.2174/1381612826666200707121636

Price: $65

conference banner
Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized.

Methods: The present review discusses the recent repurposing of drugs for COVID-19 treatment.

Results: Several compounds, including remdesivir, lopinavir, ritonavir, interferon-β, ribavirin, chloroquine/ hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response.

Conclusion: Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.

Keywords: Azithromycin, chloroquine, ivermectin, lopinavir, remdesivir, ribavirin.

« Previous Next »
[1]
WHO - World Health Organization. Novel Coronavirus (2019-nCoV): Situation report, 12. World Health Organization 2020.
[2]
Sohrabi C, Alsafi Z, O’Neill N, et al. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). Int J Surg 2020; 26: 17-76.
[http://dx.doi.org/10.1016/j.ijsu.2020.02.034]
[3]
Rodriguez-Morales AJ, Bonilla-Aldana DK, Balbin-Ramon GJ, et al. History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus. Infez Med 2020; 28: 3-5.
[PMID: 32009128]
[4]
Channappanavar R, Zhao J, Perlman S. T cell-mediated immune response to respiratory coronaviruses. Immunol Res 2014; 59(1-3): 118-28.
[http://dx.doi.org/10.1007/s12026-014-8534-z] [PMID: 24845462]
[5]
Rabi FA, Al Zoubi MS, Kasasbeh GA, Salameh DM, Al-Nasser AD. SARS-CoV-2 and Coronavirus disease 2019: What we know so far. Pathogens 2020; 9(3): 231.
[http://dx.doi.org/10.3390/pathogens9030231] [PMID: 32245083]
[6]
Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020; 215108427
[http://dx.doi.org/10.1016/j.clim.2020.108427] [PMID: 32325252]
[7]
Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4.
[http://dx.doi.org/10.1038/nature02145] [PMID: 14647384]
[8]
Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020; 14(2): 185-92.
[http://dx.doi.org/10.1007/s11684-020-0754-0] [PMID: 32170560]
[9]
Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 2020; 87(4): 281-6.
[http://dx.doi.org/10.1007/s12098-020-03263-6] [PMID: 32166607]
[10]
Bonilla-Aldana DK, Dhama K, Rodriguez-Morales AJ. Revisiting the one health approach in the context of COVID-19: a look into the ecology of this emerging disease. Advances in Animal and Veterinary Science 2020; 8: 234-7.
[http://dx.doi.org/10.17582/journal.aavs/2020/8.3.234.237]
[11]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[12]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[13]
Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: Summary of a report of 72-314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020; 323(13): 1239-42.
[http://dx.doi.org/10.1001/jama.2020.2648] [PMID: 32091533]
[14]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[15]
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323: 1061-9.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[16]
Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents 2020; 55(3)105924
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105924] [PMID: 32081636]
[17]
Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically Ill patients with COVID-19 in Washington State. JAMA 2020.
[http://dx.doi.org/10.1001/jama.2020.4326] [PMID: 32191259]
[18]
Jin Y, Wang M, Zuo Z, et al. Diagnostic value and dynamic variance of serum antibody in coronavirus disease 2019. Int J Infect Dis 2019; 94: 49-52.
[19]
Huang P, Liu T, Huang L, et al. Use of chest CT in combination with negative RT-PCR assay for the 2019 novel coronavirus but high clinical suspicion. Radiology 2020; 295(1): 22-3.
[http://dx.doi.org/10.1148/radiol.2020200330] [PMID: 32049600]
[20]
Ahn DG, Shin HJ, Kim MH, et al. Current status of epidemiology, diagnosis, therapeutics, and vaccines for novel coronavirus disease 2019 (COVID-19). J Microbiol Biotechnol 2020; 30(3): 313-24.
[http://dx.doi.org/10.4014/jmb.2003.03011] [PMID: 32238757]
[21]
Mardani R, Ahmadi Vasmehjani A, Zali F, et al. Laboratory parameters in detection of COVID-19 patients with positive RT-PCR; a diagnostic accuracy study. Arch Acad Emerg Med 2020; 8(1)e43
[PMID: 32259132]
[22]
Jin YH, Cai L, Cheng ZS, et al. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-NCOV) infected pneumonia (standard version). Mil Med Res 2020; 7(1): 4.
[http://dx.doi.org/10.1186/s40779-020-0233-6] [PMID: 32029004]
[23]
Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. MedRxiv 2020.
[24]
Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock. Intensive Care Med 2017; 43(3): 304-77.
[http://dx.doi.org/10.1007/s00134-017-4683-6] [PMID: 28101605]
[25]
Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chin Med J (Engl) 2020; 133(9): 1025-31.
[http://dx.doi.org/10.1097/CM9.0000000000000744] [PMID: 32044814]
[26]
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395(10223): 473-5.
[http://dx.doi.org/10.1016/S0140-6736(20)30317-2] [PMID: 32043983]
[27]
WHO - World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected 2020.
[28]
Zhao JP, Hu Y, Du RH, et al. Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43(0)E007
[PMID: 32034899]
[29]
Martinez MA. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemother 2020; 64(5): e00399-20.
[http://dx.doi.org/10.1128/AAC.00399-20] [PMID: 32152082]
[30]
Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci 2020; 50(SI-1): 611-9.
[http://dx.doi.org/10.3906/sag-2004-145] [PMID: 32293834]
[31]
Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020; 92(4): 418-23.
[http://dx.doi.org/10.1002/jmv.25681] [PMID: 31967327]
[32]
Ko WC, Rolain JM, Lee NY, et al. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int J Antimicrob Agents 2020; 55(4)105933
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105933] [PMID: 32147516]
[33]
Zhang DH, Wu KL, Zhang X, Deng SQ, Peng B. In silico screening of Chinese herbal medicines with the potential to directly inhibit 2019 novel coronavirus. J Integr Med 2020; 18(2): 152-8.
[http://dx.doi.org/10.1016/j.joim.2020.02.005] [PMID: 32113846]
[34]
Mercorelli B, Palù G, Loregian A. Drug repurposing for viral infectious diseases: How far are we? Trends Microbiol 2018; 26(10): 865-76.
[http://dx.doi.org/10.1016/j.tim.2018.04.004] [PMID: 29759926]
[35]
Pushpakom S, Iorio F, Eyers PA, et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 2019; 18(1): 41-58.
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[36]
Maxmen A. Slew of trials launch to test coronavirus treatments in China. Nature 2020; 78: 37-348.
[37]
Rosa SGV, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Rev Panam Salud Publica 2020; 44e40
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID: 32256547]
[38]
Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio 2018; 9(2): e00221-18.
[http://dx.doi.org/10.1128/mBio.00221-18] [PMID: 29511076]
[39]
Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9(396): 396.
[http://dx.doi.org/10.1126/scitranslmed.aal3653] [PMID: 28659436]
[40]
Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res 2019; 169104541
[http://dx.doi.org/10.1016/j.antiviral.2019.104541] [PMID: 31233808]
[41]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30(3): 269-71.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[42]
Gralinski LE, Bankhead A III, Jeng S, et al. Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. MBio 2013; 4(4): e00271-13.
[http://dx.doi.org/10.1128/mBio.00271-13] [PMID: 23919993]
[43]
Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 2016; 531(7594): 381-5.
[http://dx.doi.org/10.1038/nature17180] [PMID: 26934220]
[44]
Holshue ML, DeBolt C, Lindquist S, et al. Washington State 2019-nCoV case investigation team. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020; 382(10): 929-36.
[http://dx.doi.org/10.1056/NEJMoa2001191] [PMID: 32004427]
[45]
Mulangu S, Dodd LE, Davey RT Jr, et al. PALM Writing Group. PALM Consortium Study Team. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 2019; 381(24): 2293-303.
[http://dx.doi.org/10.1056/NEJMoa1910993] [PMID: 31774950]
[46]
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020; 395(10236): 1569-78.
[http://dx.doi.org/10.1016/S0140-6736(20)31022-9] [PMID: 32423584]
[47]
Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunol Rev 2004; 202: 8-32.
[http://dx.doi.org/10.1111/j.0105-2896.2004.00204.x] [PMID: 15546383]
[48]
Davidson S, Maini MK, Wack A. Disease-promoting effects of type I interferons in viral, bacterial, and coinfections. J Interferon Cytokine Res 2015; 35(4): 252-64.
[http://dx.doi.org/10.1089/jir.2014.0227] [PMID: 25714109]
[49]
Markowitz CE. Interferon-beta: mechanism of action and dosing issues. Neurology 2007; 68(24)(Suppl. 4): S8-S11.
[http://dx.doi.org/10.1212/01.wnl.0000277703.74115.d2] [PMID: 17562848]
[50]
Sarzi-Puttini P, Giorgi V, Sirotti S, et al. COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol 2020; 38(2): 337-42.
[PMID: 32202240]
[51]
Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag 2008; 4(5): 1023-33.
[PMID: 19209283]
[52]
Chu CM, Cheng VC, Hung IF, et al. HKU/UCH SARS Study Group. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59(3): 252-6.
[http://dx.doi.org/10.1136/thorax.2003.012658] [PMID: 14985565]
[53]
Chan JF, Yao Y, Yeung ML, et al. Treatment with lopinavir/ritonavir or interferon-beta1b improves outcome of MERS-CoV infection in a nonhuman primate model of common Marmoset. J Infect Dis 2015; 212(12): 1904-13.
[http://dx.doi.org/10.1093/infdis/jiv392] [PMID: 26198719]
[54]
Arabi YM, Alothman A, Balkhy HH, et al. And the MIRACLE trial group. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial. Trials 2018; 19(1): 81.
[http://dx.doi.org/10.1186/s13063-017-2427-0] [PMID: 29382391]
[55]
Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020; 382(19): 1787-99.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[56]
Thomas E, Ghany MG, Liang TJ. The application and mechanism of action of ribavirin in therapy of hepatitis C. Antivir Chem Chemother 2012; 23(1): 1-12.
[http://dx.doi.org/10.3851/IMP2125] [PMID: 22592135]
[57]
Chen F, Chan KH, Jiang Y, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004; 31(1): 69-75.
[http://dx.doi.org/10.1016/j.jcv.2004.03.003] [PMID: 15288617]
[58]
Booth CM, Matukas LM, Tomlinson GA, et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289(21): 2801-9.
[http://dx.doi.org/10.1001/jama.289.21.JOC30885] [PMID: 12734147]
[59]
Knowles SR, Phillips EJ, Dresser L, Matukas L. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis 2003; 37(8): 1139-42.
[http://dx.doi.org/10.1086/378304] [PMID: 14523782]
[60]
Morgenstern B, Michaelis M, Baer PC, Doerr HW, Cinatl J Jr. Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun 2005; 326(4): 905-8.
[http://dx.doi.org/10.1016/j.bbrc.2004.11.128] [PMID: 15607755]
[61]
Falzarano D, de Wit E, Martellaro C, Callison J, Munster VJ, Feldmann H. Inhibition of novel β coronavirus replication by a combination of interferon-α2b and ribavirin. Sci Rep 2013; 3: 1686.
[http://dx.doi.org/10.1038/srep01686] [PMID: 23594967]
[62]
Arabi YM, Shalhoub S, Mandourah Y, et al. Ribavirin and interferon therapy for critically ill patients with middle east respiratory syndrome: a multicenter observational study. Clin Infect Dis 2019; 544.
[http://dx.doi.org/10.1093/cid/ciz544] [PMID: 31925415]
[63]
McCreary EK, Pogue JM. COVID-19 treatment: a review of early and emerging options. Oxford University Press 2020.
[64]
Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, Kirk K. Chloroquine transport via the malaria parasite’s chloroquine resistance transporter. Science 2009; 325(5948): 1680-2.
[http://dx.doi.org/10.1126/science.1175667] [PMID: 19779197]
[65]
Ridley RG, Hofheinz W, Matile H, et al. 4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant Plasmodium falciparum. Antimicrob Agents Chemother 1996; 40(8): 1846-54.
[http://dx.doi.org/10.1128/AAC.40.8.1846] [PMID: 8843292]
[66]
Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol 2020; 16(3): 155-66.
[http://dx.doi.org/10.1038/s41584-020-0372-x] [PMID: 32034323]
[67]
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.
[http://dx.doi.org/10.1016/j.ijantimicag.2007.05.015] [PMID: 17629679]
[68]
Devaux CA, Rolain JM, Colson P, Raoult D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int J Antimicrob Agents 2020; 55(5)105938
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[69]
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(11): 722-7.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[70]
Tsiang H, Superti F. Ammonium chloride and chloroquine inhibit rabies virus infection in neuroblastoma cells. Brief report. Arch Virol 1984; 81(3-4): 377-82.
[http://dx.doi.org/10.1007/BF01310010] [PMID: 6148053]
[71]
Kronenberger P, Vrijsen R, Boeyé A. Chloroquine induces empty capsid formation during poliovirus eclipse. J Virol 1991; 65(12): 7008-11.
[http://dx.doi.org/10.1128/JVI.65.12.7008-7011.1991] [PMID: 1658391]
[72]
Boelaert JR, Piette J, Sperber K. The potential place of chloroquine in the treatment of HIV-1-infected patients. J Clin Virol 2001; 20(3): 137-40.
[http://dx.doi.org/10.1016/S1386-6532(00)00140-2] [PMID: 11166662]
[73]
Tsai WP, Nara PL, Kung HF, Oroszlan S. Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses 1990; 6(4): 481-9.
[http://dx.doi.org/10.1089/aid.1990.6.481] [PMID: 1692728]
[74]
Savarino A, Gennero L, Sperber K, Boelaert JR. The anti-HIV-1 activity of chloroquine. J Clin Virol 2001; 20(3): 131-5.
[http://dx.doi.org/10.1016/S1386-6532(00)00139-6] [PMID: 11166661]
[75]
Romanelli F, Smith KM, Hoven AD. Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity. Curr Pharm Des 2004; 10(21): 2643-8.
[http://dx.doi.org/10.2174/1381612043383791] [PMID: 15320751]
[76]
Superti F, Seganti L, Orsi N, Divizia M, Gabrieli R, Panà A. The effect of lipophilic amines on the growth of hepatitis A virus in Frp/3 cells. Arch Virol 1987; 96(3-4): 289-96.
[http://dx.doi.org/10.1007/BF01320970] [PMID: 2821967]
[77]
Bishop NE. Practical guidelines in antiviral therapy. International Virology 1998; 41: 261-71.
[78]
Mizui T, Yamashina S, Tanida I, et al. Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy. J Gastroenterol 2010; 45(2): 195-203.
[http://dx.doi.org/10.1007/s00535-009-0132-9] [PMID: 19760134]
[79]
Yan Y, Zou Z, Sun Y, et al. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res 2013; 23(2): 300-2.
[http://dx.doi.org/10.1038/cr.2012.165] [PMID: 23208422]
[80]
Coombs K, Mann E, Edwards J, Brown DT. Effects of chloroquine and cytochalasin B on the infection of cells by Sindbis virus and vesicular stomatitis virus. J Virol 1981; 37(3): 1060-5.
[http://dx.doi.org/10.1128/JVI.37.3.1060-1065.1981] [PMID: 6262524]
[81]
Delogu I, de Lamballerie X. Chikungunya disease and chloroquine treatment. J Med Virol 2011; 83(6): 1058-9.
[http://dx.doi.org/10.1002/jmv.22019] [PMID: 21503920]
[82]
De Lamballerie X, Boisson V, Reynier JC, et al. On chikungunya acute infection and chloroquine treatment. Vector Borne Zoonotic Dis 2008; 8(6): 837-9.
[http://dx.doi.org/10.1089/vbz.2008.0049] [PMID: 18620511]
[83]
Khan M, Santhosh SR, Tiwari M, Lakshmana Rao PV, Parida M. Assessment of in vitro prophylactic and therapeutic efficacy of chloroquine against Chikungunya virus in vero cells. J Med Virol 2010; 82(5): 817-24.
[http://dx.doi.org/10.1002/jmv.21663] [PMID: 20336760]
[84]
Randolph VB, Winkler G, Stollar V. Acidotropic amines inhibit proteolytic processing of flavivirus prM protein. Virology 1990; 174(2): 450-8.
[http://dx.doi.org/10.1016/0042-6822(90)90099-D] [PMID: 2154882]
[85]
Farias KJ, Machado PR, de Almeida Junior R.F., de Aquino AA, da Fonseca BA. Chloroquine interferes with dengue-2 virus replication in U937 cells. Microbiol Immunol 2014; 58(6): 318-26.
[http://dx.doi.org/10.1111/1348-0421.12154] [PMID: 24773578]
[86]
Li C, Zhu X, Ji X, et al. Chloroquine, a FDA-approved drug, prevents zika virus infection and its associated congenital microcephaly in mice. EBioMedicine 2017; 24: 189-94.
[http://dx.doi.org/10.1016/j.ebiom.2017.09.034] [PMID: 29033372]
[87]
Delvecchio R, Higa LM, Pezzuto P, et al. Chloroquine, an endocytosis blocking agent, inhibits Zika virus infection in different cell models. Viruses 2016; 8(12)e322
[http://dx.doi.org/10.3390/v8120322] [PMID: 27916837]
[88]
Dowall SD, Bosworth A, Watson R, et al. Chloroquine inhibited Ebola virus replication in vitro but failed to protect against infection and disease in the in vivo guinea pig model. J Gen Virol 2015; 96(12): 3484-92.
[http://dx.doi.org/10.1099/jgv.0.000309] [PMID: 26459826]
[89]
Kouroumalis EA, Koskinas J. Treatment of chronic active hepatitis B (CAH B) with chloroquine: a preliminary report. Ann Acad Med Singapore 1986; 15(2): 149-52.
[PMID: 3752892]
[90]
Koyama AH, Uchida T. Inhibition of multiplication of herpes simplex virus type 1 by ammonium chloride and chloroquine. Virology 1984; 138(2): 332-5.
[http://dx.doi.org/10.1016/0042-6822(84)90356-8] [PMID: 6093369]
[91]
Yao X, Ye F, Zhang M, 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; 71(15): 732-9.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[92]
Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005; 2: 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[93]
Fox RI. Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 1993; 23(2)(Suppl. 1): 82-91.
[http://dx.doi.org/10.1016/S0049-0172(10)80012-5] [PMID: 8278823]
[94]
Biot C, Daher W, Chavain N, et al. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J Med Chem 2006; 49(9): 2845-9.
[http://dx.doi.org/10.1021/jm0601856] [PMID: 16640347]
[95]
Keyaerts E, Li S, Vijgen L, et al. Antiviral activity of chloroquine against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother 2009; 53(8): 3416-21.
[http://dx.doi.org/10.1128/AAC.01509-08] [PMID: 19506054]
[96]
de Wilde AH, Jochmans D, Posthuma CC, 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.
[http://dx.doi.org/10.1128/AAC.03011-14] [PMID: 24841269]
[97]
Cong Y, Hart BJ, Gross R, et al. MERS-CoV pathogenesis and antiviral efficacy of licensed drugs in human monocyte-derived antigen-presenting cells. PLoS One 2018; 13(3)e0194868
[http://dx.doi.org/10.1371/journal.pone.0194868] [PMID: 29566060]
[98]
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): 72-3.
[http://dx.doi.org/10.5582/bst.2020.01047] [PMID: 32074550]
[99]
Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial 2020.
[100]
Liu X, Chen H, Shang Y, et al. Efficacy of chloroquine and lopinavir/ritonavir in mild/general COVID-2019: a prospective, open-label, multicenter randomized controlled clinical study. Research Square 2020.
[http://dx.doi.org/10.21203/rs.3.rs-16392/v1]
[101]
Mandeep R. Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet 2020. Online ahead of print.
[http://dx.doi.org/10.1016/S0140-6736(20)31180-6]
[102]
Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with COVID-19. N Engl J Med 2020; 382(25): 2411-8.
[http://dx.doi.org/10.1056/NEJMoa2012410] [PMID: 32379955]
[103]
Cortegiani A, Ingoglia G, Ippolito M, Giarratano A, Einav S. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Critical Care 2020; S0883-9441(20): 30390-7.
[104]
Contopoulos-Ioannidis DG, Ioannidis JP, Chew P, Lau J. Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. J Antimicrob Chemother 2001; 48(5): 691-703.
[http://dx.doi.org/10.1093/jac/48.5.691] [PMID: 11679558]
[105]
Retsema J, Fu W. Macrolides: structures and microbial targets. Int J Antimicrob Agents 2001; 18(Suppl. 1): S3-S10.
[http://dx.doi.org/10.1016/S0924-8579(01)00401-0] [PMID: 11574188]
[106]
Madrid PB, Panchal RG, Warren TK, et al. Evaluation of Ebola virus inhibitors for drug repurposing. ACS Infect Dis 2015; 1(7): 317-26.
[http://dx.doi.org/10.1021/acsinfecdis.5b00030] [PMID: 27622822]
[107]
Retallack H, Di Lullo E, Arias C, et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proc Natl Acad Sci USA 2016; 113(50): 14408-13.
[http://dx.doi.org/10.1073/pnas.1618029113] [PMID: 27911847]
[108]
Bacharier LB, Guilbert TW, Mauger DT, et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: A randomized clinical trial. JAMA 2015; 314(19): 2034-44.
[http://dx.doi.org/10.1001/jama.2015.13896] [PMID: 26575060]
[109]
Gautret P, Lagier JC, Parola 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 2020.105949
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105949] [PMID: 32205204]
[110]
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39(5): 529-39.
[http://dx.doi.org/10.1007/s00281-017-0629-x] [PMID: 28466096]
[111]
Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV infected mice. Cell Host Microbe 2016; 19(2): 181-93.
[http://dx.doi.org/10.1016/j.chom.2016.01.007] [PMID: 26867177]
[112]
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124(2): 188-95.
[http://dx.doi.org/10.1182/blood-2014-05-552729] [PMID: 24876563]
[113]
Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm 2008; 65(15): 1413-8.
[http://dx.doi.org/10.2146/ajhp070449] [PMID: 18653811]
[114]
Zhang Q, Wang Y, Qi C, Shen L, Li J. Clinical trial analysis of 2019‐nCoV therapy registered in China. J Med Virol 2020; 1-6.
[http://dx.doi.org/10.1002/jmv.25733]
[115]
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 2020; 19; 117(20): 10970-5.
[116]
SIMIT. Vademecum per la cura delle persone con malattia da COVI-19 2020.
[117]
Campbell WC. History of avermectin and ivermectin, with notes on the history of other macrocyclic lactone antiparasitic agents. Curr Pharm Biotechnol 2012; 13(6): 853-65.
[http://dx.doi.org/10.2174/138920112800399095] [PMID: 22039784]
[118]
González Canga A, Sahagún Prieto AM, Diez Liébana MJ, et al. The pharmacokinetics and interactions of ivermectin in humans--a mini-review. AAPS J 2008; 10(1): 42-6.
[http://dx.doi.org/10.1208/s12248-007-9000-9] [PMID: 18446504]
[119]
Muñoz J, Ballester MR, Antonijoan RM, et al. Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers. PLoS Negl Trop Dis 2018; 12(1)e0006020
[http://dx.doi.org/10.1371/journal.pntd.0006020] [PMID: 29346388]
[120]
Raza S, Shahin F, Zhai W, et al. Ivermectin inhibits bovine herpesvirus 1 DNA polymerase nuclear import and interferes with viral replication. Microoroanisms 2020; 8E409
[121]
Ketkar H, Yang L, Wormser GP, Wang P. Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system. Diagn Microbiol Infect Dis 2019; 95(1): 38-40.
[http://dx.doi.org/10.1016/j.diagmicrobio.2019.03.012] [PMID: 31097261]
[122]
Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J 2012; 443(3): 851-6.
[http://dx.doi.org/10.1042/BJ20120150] [PMID: 22417684]
[123]
Tay MY, Fraser JE, Chan WK, et al. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Res 2013; 99(3): 301-6.
[http://dx.doi.org/10.1016/j.antiviral.2013.06.002] [PMID: 23769930]
[124]
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178104787
[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[125]
Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res 2020; 177104760
[http://dx.doi.org/10.1016/j.antiviral.2020.104760] [PMID: 32135219]

Rights & Permissions Print Cite
Article Metrics
82
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy