COVID-19: well-known drugs, new opportunities

View or download the full article: 
PDF icon health-risk-analysis-2020-4-19.pdf
UDC: 
614.40: 615.7
DOI: 
10.21668/health.risk/2020.4.19.eng
Authors: 

A.Kh. Ashirmetov1, I.R. Mavlyanov2, Z.I. Mavlyanov2, G.Zh. Zharylkasynova3

Organization: 

1Uzbekistan’s Public Healthcare Ministry, 26 Spitamena Str., Tashkent, 100121, Uzbekistan
2Tashkent Institute for Post-Graduate Medical Education, 12 Sharafa Ave., Tashkent, 100000, Uzbekistan
3Bukhara State Medical Institute named after Abu Ali ibn Sino, 1 Navoi Ave., Bukhara, 200118, Uzbekistan

Abstract: 

Up to now, coronavirus infection that causes an acute respiratory syndrome has been detected almost in all countries worldwide. Global spread of SARS-CoV-2 virus has become a world pandemic and there is no efficient and commonly accepted conventional therapy against COVID-19. Due to the existing emergency most drugs that can potentially be used to treat COVID-19 are allowed to be applied only basing on certain data probing their safety and efficiency against SARS-CoV. At present only Lopinavir/Ritonavir and Remdesivir are the only anti-virus drugs that are included into well-recognized management procedures for COVID-19 treatment; an acceptable alternative could probably be combined therapy that includes Hydroxychloroquine and Azithromycin. Given the existing situation, a lot of drugs that are usually used to treat other diseases are now being suggested as probable ways to treat COVID-19 taking into account all the available knowledge on pathophysiology of the infection.
In this review, basing on available data on how SARA-CoV-2 virus enters a cell and pathophysiological aspects of cytokine storm development, we have strived to highlight certain prospects related to applying anti-viral medications, anti-inflammatory and immune-suppressing drugs, vitamins and microelements that are widely used to treat and prevent various diseases. Most tested drugs as well as zinc preparations, and vitamins С and D3 turned out to have not only immune-modulating but also anti-inflammatory properties; or either they were able to block ways for the virus to enter a cell or disrupt SARS-CoV-2 intracellular replication.
Having leant from previous experience in fighting against SARS and MERS, doctors have applied some existing drugs to treat COVID-19 infections in their clinical practices; clinical tests aimed at confirming their safety and efficiency in treating COVID-19 are still being performed at the moment. Although a lot of various treatment procedures have been suggested, it is necessary to perform specifically planned randomized clinical trials based on evidence-based medicine principles, if we want to determine the most suitable ones.

Keywords: 
coronavirus, SARS-CoV-2, COVID-19, anti-viral medications, immune-modulating drugs, anti-inflammatory drugs, medications, clinical tests
Ashirmetov A.Kh., Mavlyanov I.R., Mavlyanov Z.I., Zharylkasynova G.Zh. COVID-19: well-known drugs, new opportunities. Health Risk Analysis, 2020, no. 4, pp. 170–180. DOI: 10.21668/health.risk/2020.4.19.eng
References: 
  1. Li H., Liu S.-M., Yu X.-H., Tang C.-K. Coronavirus disease 2019 (COVID-19): current status and future perspectives. International Journal of Antimicrobial Agents, 2020, vol. 55, no. 5, pp. 105951. DOI: 10.1016/j.ijantimicag.2020.105951
  2. Morse J.S., Lalonde T., Xu S., Liu W.R. Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. Chembiochem, 2020, vol. 21, no. 5, pp. 730–738. DOI: 10.1002/cbic.202000047
  3. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B. [et al.]. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med, 2020, vol. 382, no. 8, pp. 727–733. DOI: 10.1056/NEJMoa2001017
  4. Zhou P., Yang X., Wang X., Hu B., Zhang L., Zhang W., Si H.-R., Zhu Y. [et al.]. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv, 2020, no. 23, pp. 18. DOI: 10.1038/s41586-020-2012-7
  5. Chen Y., Liu Q., Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol, 2020, vol. 92, no. 4, pp. 418–423. DOI: 10.1002/jmv.25681
  6. Hoffmann M., Kleine-Weber H., Krüger N., Müller M., Drosten C., Pöhlmann S. The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells. bioRxiv, 2020, no. 31, pp. 23. DOI: 10.1101/2020.01.31.929042
  7. Qiu T., Mao T., Wang Y., Zhou M., Qiu J., Wang J., Xu J., Cao Z. Identification of potential cross-protective epitope between 2019-nCoV and SARS virus. J Genet Genom, 2020, vol. 20, no. 47 (2), pp. 115–117. DOI: 10.1016/j.jgg.2020.01.003
  8. Perricone C., Triggianese P., Bartoloni E., Cafaro G., Bonifacio A.F., Bursi R., Perricone R., Gerli R. The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19 Journal of Autoimmunity. Journal of Autoimmunity, 2020, vol. 111, pp. 102468. DOI: 10.1016/j.jaut.2020.102468
  9. Zhang W., Zhao Y., Zhang F., Wang Q., Li T., Liu Z., Wang J., Qin Y. [et al.]. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology, 2020, no. 214, pp. 108393. DOI: 10.1016/j.clim.2020.108393
  10. Favallia E.G., Ingegnoli F., De Lucia O., Cincinelli G., Cima R., Caporali R. COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimmunity Reviews, 2020, vol. 19, no. 5, pp. 102523. DOI: 10.1016/j.autrev.2020.102523
  11. Geng Y.-J., Wei Z.-Y., Qian H.-Y., Huang J., Lodato R., Castriotta R.J. [et al.]. Castriotta Pathophysiological Characteristics and Therapeutic Approaches for Pulmonary Injury and Cardiovascular Complications of Coronavirus Disease 2019. Cardiovascular Pathology, 2020, no. 47, pp. 107228. DOI: 10.1016/j.carpath.2020.107228
  12. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J., HLH Across Speciality Collaboration. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet, 2020, vol. 28, no. 395 (10229), pp. 1033–1034. DOI: 10.1016/S0140-6736(20)30628-0
  13. Pedersen S.F., Ho Y.C. SARS-CoV-2: a storm is raging. J. Clin. Invest, 2020, vol. 1, no. 130 (5), pp. 2202–2205. DOI: 10.1172/JCI137647
  14. Li G., Fan Y., Lai Y., Han T., Li Z., Zhou P., Pan P., Wang W. [et al.]. Coronavirus infections and immune responses. J. Med. Virol, 2020, vol. 92, no. 4, pp. 424–432. DOI: 10.1002/jmv.25685
  15. Zumla A., Chan J.F., Azhar E.I., Hui D.S.C., Yuen K.-Y. Coronaviruses – drug discovery and therapeutic options. Nat Rev Drug Discov, 2016, vol. 15, no. 5, pp. 327–347. DOI: 10.1038/nrd.2015.37
  16. Martinez M.A. Compounds with therapeutic potential against novel respiratory 2019 coronavirus. Antimicrob Agents Chemother, 2020, vol. 64, no. 5, pp. 7. DOI: 10.1128/AAC.00399-20
  17. Elfiky A.A. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci, 2020, vol. 15, no. 253, pp. 117592. DOI: 10.1016/j.lfs.2020.117592
  18. Li H., Wang Y.M., Xu J.Y., Cao B. Potential antiviral therapeutics for 2019 Novel Coronavirus. Chin J Tuberc Respir Dis, 2020, vol. 5, no. 43 (0), pp. E002. DOI: 10.3760/cma.j.issn.1001-0939.2020.0002
  19. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J., Wang B., Xiang H. [et al.]. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, vol. 17, no. 323 (11), pp. 1061–1069. DOI: 10.1001/jama.2020.1585
  20. Arabi Y.M., Asiri A.Y., Assiri A.M., Jokhdar H.A.A., Alothman A., Balkhy H.H., Aljohani S., Al Harbi S. [et al.]. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials, 2020, vol. 3, no. 21 (1), pp. 8. DOI: 10.1186/s13063-019-3846-x
  21. Lim J., Jeon S., Shin H.Y., Kim M.J., Seong Y.M., Lee W.J., Choe K.W., Kang Y.M., Lee B., S.J. Park Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci, 2020, vol. 17, no. 35(6), pp. e79. DOI: 10.3346/jkms.2020.35.e79
  22. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M., Shi Z., Hu Z., Zhong W., Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res, 2020, vol. 30, no. 3, pp. 269–271. DOI: 10.1038/s41422-020-0282-0
  23. Jordan P.C., Stevens S.K., Deval J. Nucleosides for the treatment of respiratory RNA virus infections. Antivir Chem Chemother, 2018, vol. 26, pp. 1631083325.
  24. Cao Yu-C., Deng Q.-X., Dai S.-X. Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence. Travel Medicine and Infectious Disease, 2020, vol. 35, pp. 101647. DOI: 10.1016/j.tmaid.2020.101647
  25. Dong L., Hu S., Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug discoveries & therapeutics, 2020, vol. 14, no. 1, vol. 58–60. DOI: 10.5582/ddt.2020.01012
  26. Elfiky A.A. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sciences, 2020, vol. 1, no. 248, pp. 117477. DOI: 10.1016/j.lfs.2020.117477
  27. Khamitov R.A., Loginova S., Shchukina V.N., Borisevich S.V., Maksimov V.A., Shuster A.M. Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures. Vopr Virusol, 2008, vol. 53, no. 4, pp. 9–13.
  28. Wang Z., Chen X., Lu Y., Chen F., Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Biosci Trends, 2020, vol. 16, no. 14 (1), pp. 64–68. DOI: 10.5582/bst.2020.01030
  29. Harrison C. Coronavirus puts drug repurposing on the fast track. Nature biotechnology, 2020, vol. 38, no. 4, pp. 389–381. DOI: 10.1038/d41587-020-00003-1
  30. Chan K.W., Wong V.T., Tang S.C.W. COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease. Am J Chin Med, 2020, vol. 48, no. 3, pp. 737–762. DOI: 10.1142/S0192415X20500378
  31. Hellmich B., Agueda A., Monti S., Buttgereit F., de Boysson H., Brouwer E., Cassie R., Cid M.C. [et al.]. Update of the EULAR recommendations for the management of large vessel vasculitis. Ann. Rheum. Dis, 2020, vol. 79, no. 1, pp. 19–30. DOI: 10.1136/annrheumdis-2019-215672
  32. Fanouriakis A., Kostopoulou M., Alunno A., Aringer M., Bajema I., Boletis J.N., Cervera R., Doria A. [et al.]. Update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann. Rheum. Dis, 2019, vol. 78, no. 6, pp. 736–745. DOI: 10.1136/annrheumdis-2019-215089
  33. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Centers for Disease Control and Prevention, 2020, pp. 13.
  34. Shukla A.M., Shukla А.W. Expanding horizons for clinical applications of chloroquine, hydroxychloroquine, and related structural analogues. Drugs Context, 2019, vol. 25, no. 8, pp. 12. DOI: 10.7573/dic.2019-9-1
  35. Colson P., Rolain J.-M., Lagier J.-C., Brouqui P., Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int. J. Antimicrob, 2020, vol. 55, no. 4, pp. 105932. DOI: 10.1016/j.ijantimicag.2020.105932
  36. Vincent M.J., Bergeron E., Benjannet S., Erickson B.R., Rollin P.E., Ksiazek T.G., Seidah N.G., Nichol S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J, 2005, no. 2, pp. 69. DOI: 10.1186/1743-422X-2-69
  37. Multicenter collaboration group of Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia. Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi, 2020, vol. 20, no. 43, pp. E019.
  38. Vademecum per la cura delle persone con malattia da COVID-19 – versione 2.0 2020. SIMIT Societa Italiana di Malattie Infettive e Tropicali Sezione regione Lombardia, 2020, 2 p.
  39. Touret F., de Lamballerie X. Of chloroquine and COVID-19. Antiviral Res, 2020, no. 177, pp. 104762. DOI: 10.1016/j.antiviral.2020.104762
  40. 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. Crit. Care, 2020, no. 57, pp. 279–283. DOI: 10.1016/j.jcrc.2020.03.005
  41. Melles R.B., Marmor M.F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol, 2014, vol. 132, no. 12, pp. 1453–1460. DOI: 10.1001/jamaophthalmol.2014.3459
  42. Sarma P., Kaur H., Kumar H., Mahendru D., Avti P., Bhattacharyya A., Prajapat M., Shekhar N. [et al.]. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis. J. Med. Virol, 2020, vol. 92, no. 7, pp. 776–785. DOI: 10.1002/jmv.25898
  43. Gautret P., Lagier J., Parola P., Hoang V.T., Meddeb L., Mailhe M., Doudier B., Courjon J. [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, vol. 56, no. 1, pp. 105949. DOI: 10.1016/j.ijantimicag.2020.105949
  44. Dilly S., Fotso Fotso A., Lejal N., Zedda G., Chebbo M., Rahman F., Companys S., Bertrand H.C. [et al.]. From naproxen repurposing to naproxen analogues and their antiviral activity against influenza A virus. J. Med. Chem, 2018, vol. 61, no. 16, pp. 7202–7217. DOI: 10.1021/acs.jmedchem.8b00557
  45. Qiao W., Wang C., Chen B., Zhang F., Liu Y., Lu Q., Guo H., Yan C. [et al.]. Ibuprofen attenuates cardiac fibrosis in Streptozotocin-induced diabetic rats. Cardiology, 2015, vol. 131, no. 2, pp. 97–106. DOI: 10.1159/000375362
  46. Adnet F., Clama Schwok A. Efficacy of Addition of Naproxen in the Treatment of Critically Ill Patients Hospitalized for COVID-19 Infection (ENACOVID). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT04325633 (12.05.2020).
  47. Little P. Non-steroidal anti-inflammatory drugs and COVID-19. BMJ, 2020, no. 27, pp. 368:m1185. DOI: 10.1136/bmj.m1185
  48. Kotch C., Barrett D., Teachey D.T. Tocilizumab for the treatment of chimeric antigen receptor T cell-induced cytokine release syndrome. Expert review of clinical immunology, 2019, vol. 15, no. 8, pp. 813–822. DOI: 10.1080/1744666X.2019.1629904
  49. Richardson P., Griffin I., Tucker C., Smith D., Oechsle O., Phelan A., Rawling M., Savory E., Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet, 2020, vol. 395, no. 10223, pp. e30–e31. DOI: 10.1016/S0140-6736(20)30304-4
  50. Matsuyama S., Nao N., Shirato K., Kawase M., Saito S., Takayama I., Nagata N., Sekizuka T. [et al.]. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proceedings of the National Academy of Sciences, 2020, vol. 31, no. 117 (13), pp. 7001–7003. DOI: 10.1073/pnas.2002589117
  51. Gordon D.E., Jang G.M., Bouhaddou M., Xu J., Obernier K., O’Meara M.J., Guo J.Z., Swaney D.L. [et al.]. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing. BioRxiv, 2020, vol. 27, pp. 45. DOI: 10.1101/2020.03.22.002386
  52. Farouka A., Salmanb S. Dapsone and doxycycline could be potential treatment modalities for COVID-19. Medical Hypotheses, 2020, no. 140, pp. 109768. DOI: 10.1016/j.mehy.2020.109768
  53. Altschulera Е.L., Kast R.E. Dapsone, colchicine and olanzapine as treatment adjuncts to prevent COVID-19 associated adult respiratory distress syndrome (ARDS). Medical Hypotheses, 2020, no. 141, pp. 109774. DOI: 10.1016/j.mehy.2020.109774
  54. Zhang L., Liu Y. Potential interventions for novel coronavirus in China: a systematic review. Journal of medical virology, 2020, vol. 92, no. 5, pp. 479–490. DOI: 10.1002/jmv.25707
  55. Grant W.B., Lahore H., McDonnell S.L., Baggerly C.A., French C.B., Aliano J.L., Bhattoa H.P. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 2020, vol. 12, no. 4, pp. E988. DOI: 10.3390/nu12040988
  56. Aranow C. Vitamin D and the immune system. J. Investig. Med, 2011, vol. 59, no. 6, pp. 881–886. DOI: 10.231/JIM.0b013e31821b8755
  57. Nair R., Maseeh A. Vitamin D. The «sunshine» vitamin. J Pharmacol Pharmacother, 2012, vol. 3, no. 2, pp. 118–126. DOI: 10.4103/0976-500X.95506
  58. Kennel K.A., Drake M.T., Hurley D.L. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc, 2010, vol. 85, no. 8, pp. 752–757. DOI: 10.4065/mcp.2010.0138
  59. Nonnecke B., McGill J., Ridpath J., Sacco R.E., Lippolis J.D., Reinhardt T.A. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves. Journal of dairy science, 2014, vol. 97, no. 9, pp. 5566–5579. DOI: 10.3168/jds.2014-8293
  60. Martineau A.R., Jolliffe D.A., Hooper R.L., Greenberg L., Aloia J.F., Bergman P., Dubnov-Raz G., Esposito S. [et al.]. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ, 2017, vol. 15, no. 356, pp. i6583. DOI: 10.1136/bmj.i6583
  61. Wimalawansa S.J. Reducing Risks from COVID-19: Cost-Effective Ways of Strengthening Individual’s and the Population Immunity with Vitamin D. J Endocrinol Sci, 2020, vol. 2, no. 2, pp. 5–13.
  62. Lechien J.R., Chiesa-Estomba C.M., De Siati D.R., Horoi M., Le Bon S.D., Rodriguez A., Dequanter D., Blecic S. [et al.]. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur. Arch. Otorhinolaryngol, 2020, vol. 277, no. 8, pp. 2251–2261. DOI: 10.1007/s00405-020-05965-1
  63. Doty R.L. Treatment for smell and taste disorders: a critical review. Handb. Clin. Neurol, 2019, no. 164, pp. 455–479. DOI: 10.1016/B978-0-444-63855-7.00025-3
Received: 
30.05.2020
Accepted: 
11.11.2020
Published: 
30.12.2020

You are here

Home