International Journal of Pharma and Bio Sciences
 
 
    ISSN 0975-6299
www.ijpbs.net
Home


REVIEW ARTICLE
Int J Pharm Bio Sci Volume 13 Issue 1, January - March, Pages:9-16

Repurposing Covid-19 Drug : Current Issues

Amartya De, Nilanjana Roy, Rajdip Saha Ankita Mukhopadhyay, Pallab dasgupta , Dipanjana Ash
DOI: http://dx.doi.org/10.22376/ijpbs.2022.13.1.P9-16
Abstract:

The deadly contagious Coronavirus disease 2019 (COVID-19) does not currently have any available treatments. As a method of discovering therapeutic agents, drug repurposing involves adapting approved and investigational drugs for new purposes. It is considered as a very effective method for drug discovery because it takes much less time and money as compared to denovo drug discovery. The aim of this study is to discuss COVID-19's repurposing efficacy, pharmacokinetics, and safety, as well as its future, the objective is to provide a to-the-point review of current literature regarding efficacy of repurposed drugs against COVID-19 and other respiratory infections caused by coronaviruses. For the review, experimental studies conducted in-silico, in-vitro, in-vivo, clinical trials in humans, case reports, and news archives were selected. A number of drugs such as favipiravir, ribavirin, lopinavir, ritonavir, darunavir, arbidol, chloroquine, hydroxychloroquine, interferons, etc have shown inhibitory effects against the SARS-CoV2invitroas well as in clinical conditions. Drugs either act by targeting virus-related mechanisms like RNA genomes, polypeptide packaging pathways, and uptake pathways, or by targeting host-related mechanisms such as angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways. Using the basic knowledge of viral pathogenesis and pharmacodynamics of drugs as well as using computational tools, many drugs are currently in pipeline to be repurposed. In the current scenario, repositioning of the drugs could be considered the new avenue for the treatment of COVID-19.In the future, these results may lead to the repurposing of drugs to treat emerging viral diseases.

Keywords: Repurposing • SARS-COV2 • COVID-19 , Coronavirus, Polypeptide Packaging Pathways, Pharmacokinetics
Full HTML:

REFERENCES

 

  1. Khadka S, Hashmi FK, Usman M. Preventing COVID-19 in low- and middle income countries. Drugs TherPerspect. 2020; 36(6):250-252. doi:https://doi.org/10.1007/s40267-020-00728-8.
  2. Coronavirus (COVID-19). WHO. 2020 [cited 2020 Jul 31]. https://who.sprinklr.com/.
  3. Strittmatter SM. Overcoming drug development bottlenecks with repurposing:Old drugs learn new tricks. Nat Med. 2014; 20(6):590-591.
  4. Roy A, Chaguturu R. Holistic Drug Targeting. In: Innovative Approaches in DrugDiscovery. 2017. Amsterdam: Elsevier, 65-88. doi:https://doi.org/10.1016/B978-0-12-801814-9.00003-9.
  5. Muralidharan N, Sakthivel R, Velmurugan D, Gromiha MM. Computationalstudies of drug repurposing and synergism of lopinavir, oseltamivir, and ritonavirbinding with SARS-CoV-2 Protease against COVID-19. J Biomol Struct Dyn.2020:1-7.
  6. Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the index patientwho caused tertiary transmission of COVID-19 infection in Korea: Theapplication of lopinavir/ritonavir for the treatment of COVID-19 infectedpneumonia monitored by quantitative RT-PCR.J Korean Med Sci. 2020; 35(6).
  7. Vankadari N. Arbidol: A potential antiviral drug for the treatment of SARSCoV-2 by blocking trimerization of the spike glycoprotein. Int J AntimicrobAgents. April 2020:56(2):105998. doi:10.1016/j.ijantimicag.2020.105998.
  8. Naveja J, Duenas-Gonzalez A, Medina-Franco J. Drug Repurposing for EpigeneticTargets Guided by Computational Methods. Academic Press; 2016. doi:https://doi.org/10.1016/B978-0-12-802808-7.00012-5.
  9. Ceccarelli M, Rullo EV, Marino A, Cacopardo B, Berretta M, NunnariG.Remdesivir effectiveness in COVID-19 and recommendations for its use. InfectDis Trop Med. 2020; 6.
  10. Huang, C, Wang, Y, Li, X, Ren, L, Zhao, J, Hu, Y, et al. Clinical features of patientsinfected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
  11. Catherine Offord. Combining the medications improved conditions in patientswith severe 2019-nCoV infections, say doctors in Thailand. TheScientist. https://www.the-scientist.com/news-opinion/flu-and-anti-hiv-drugs-show-efficacyagainst-coronavirus-67052.
  12. Ceccarelli M, Rullo EV, Marino A, Cacopardo B, Berretta M, NunnariG.Remdesivir effectiveness in COVID-19 and recommendations for its use. InfectDis Trop Med. 2020; 6.
  13. Chen C, Zhang Y, Huang J, et al. Favipiravir versus Arbidol for COVID-19: Arandomized clinical trial. 2020. doi:10.1101/2020.03.17.20037432.
  14. Cai Q, Yang M, Liu D, et al. Experimental treatment with Favipiravir for COVID-19: An open-label control study. Eng (Beijing, China). March 2020. doi:10.1016/j.eng.2020.03.007.
  15. He F, Deng Y, Li W. Coronavirus Disease 2019: What we know? J Med Virol.2020;92(7):719-725. doi:https://doi.org/10.1002/jmv.25766.
  16. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) and corona virus disease-2019 (COVID-19): Theepidemic and the challenges. Int J Antimicrob Agents. 2020; (105924).
  17. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study.Lancet. 2020;395(10223):507-513. doi:https://doi.org/10.1016/S0140-6736(20)30211-7.
  18. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019(COVID-19). Drug DiscovTher. 2020; 14(1):58-60. doi:https://doi.org/10.5582/ddt.2020.01012.
  19. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is aspecific inhibitor of importin α/β-mediated nuclear import able to inhibitreplication of HIV-1 and dengue virus. Biochem J. 2012; 443(3):851-856.
  20. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is aspecific inhibitor of importin α/β-mediated nuclear import able to inhibitreplication of HIV-1 and dengue virus. Biochem J. 2012; 443(3):851-856.
  21. Pastor M, Basas J, Vairo C, Gainza G, Moreno-Sastre M, Gomis X, et al. Safety andeffectiveness of sodium colistimethate-loaded nanostructured lipid carriers(SCM-NLC) against P. aeruginosa: In vitro and in vivo studies followingpulmonary and intramuscular administration. Nanomedicine: Nanotechnology,Biol, Med. 2019; 18:101-111. doi:https://doi.org/10.1016/j.nano.2019.02.014.
  22. Ceccarelli M, Rullo EV, Marino A, Cacopardo B, Berretta M, NunnariG.Remdesivir effectiveness in COVID-19 and recommendations for its use. InfectDis Trop Med. 2020; 6.
  23. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019(COVID-19). Drug DiscovTher. 2020; 14(1):58-60. doi:https://doi.org/10.5582/ddt.2020.01012.
  24. Peng F, Tu L, Yang Y, Hu P, Wang R, Hu Q, et al. Management and treatment ofCOVID-19: The Chinese experience. Can J Cardiol. 2020. d o i : h t t p s : / / d o i .org/10.1016/j.cjca.2020.04.010.
  25. Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N, FlorenceADER, et al. Type 1 interferons as a potential treatment against COVID-19.Antiviral Res. 2020; 178. doi:https://doi.org/10.1016/j.antiviral.2020.104791.
  26. Ceccarelli M, Rullo EV, Marino A, Cacopardo B, Berretta M, NunnariG.Remdesivir effectiveness in COVID-19 and recommendations for its use. InfectDis Trop Med. 2020; 6.Zhang J, Ma X, Yu F, Liu J, Zou F, Pan T, Zhang H. Teicoplanin potently blocks the cell entry of 2019-nCoV. bioRxiv. 2020. doi:https://doi.org/10.1101/2020.02.05.935387.
  27. Singh AK, Singh A, Shaikh A, Singh R, Misra A. Chloroquine andhydroxychloroquine in the treatment of COVID-19 with or without diabetes: Asystematic search and a narrative review with a special reference to India andother developing countries. Diabetes MetabSyndr Clin Res Rev. 2020;14(3):241-246.
  28. Liu X, Wang XJ. Potential inhibitors against 2019-nCoV coronavirus M proteasefrom clinically approved medicines. J Genet Genomics. 2020. doi:10.1016/j.jgg.2020.02.001.
  29. Cruz-Topete D, Cidlowski JA. One hormone, two actions: Anti- and proinflammatory effects of glucocorticoids. Neuroimmunomodulation. 2014;22(0):20-32. doi:10.1159/000362724.
  30. Murthy S, Gomersall CD, Fowler RA. Care for Critically Ill Patients WithCOVID-19. JAMA. 2020;323(15):1499-1500. doi:10.1001/jama.2020.3633.
  31. Parnham MJ, Haber VE, Giamarellos-Bourboulis EJ, et al. Azithromycin: mechanisms of action and their relevance for clinical applications. PharmacolTherapeut. 2014;143(2):225–245.
  32. Zimmermann P, Ziesenitz VC, Curtis N, et al. The Immunomodulatory effects of macrolides—a systematic review of the underlying mechanisms. Front Immunol. 2018;9:302.
  33. Arabi YM, Deeb AM, Al-Hameed F, et al. Macrolides in critically ill patients with Middle East respiratory syndrome. Int J Infect Dis. 2019;81:184–190.
  34. 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;56 (1):105949.
  35. Molina JM, Delaugerre C, Le Goff J, et al. No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxychloroquine and azithromycin in patients with severe COVID-19 infection. Med Mal Infect. 2020;50(4):384.
  36. Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nat Med. 2020;26(6):808–809.
  37. Chorin E, Wadhwani L, Magnani S, et al. QT interval prolongation and torsade de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin. Heart Rhythm. 2020;17 (9):1425–1433.
  38. Shin B, Park S, Kang K, et al. Self-attention based molecule representation for predicting drug-target interaction. Proc Mach Learn Res 2019; 106:230–48.
  39. Furtado RHM, Berwanger O, Fonseca HA, et al. Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial. Lancet. 2020;396(10256):959–967.
  40. Cavalcanti AB, Zampieri FG, Rosa RG, et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N Engl J Med. 2020;383(21):2041–2052.
  41. Zhang X, Zhang Y, Qiao W, et al. Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int Immunopharmacol. 2020;86:106749.
  42. Richardson P, Griffin I, Tucker C, et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020;395 (10223):E30–E31.
  43. Stebbing J, Krishnan V, de Bono S, et al. Mechanism of baricitinib supports artificial intelligence-predicted testing in COVID-19 patients. EMBO Mol Med. 2020;12:e12697.
  44. Stebbing J, Nievas GS, Falcone M, et al. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Sci Adv. 2020;eabe4724.
  45. Coronavirus (COVID-19) update: FDA authorizes drug combination for treatment of COVID-19; 2020 [cited 2020 Nov 30]. Available from: https://www.fda.gov/news-events/press-announcements/cor onavirus-covid-19-update-fda-authorizes-drug-combination- treatment-covid-19.
  46. Corticosteroids for COVID-19; 2020 [cited 2020 Oct 31].
  47. Corticosteroids in the therapy of adult patients with COVID-19; [cited 31 Oct 2020]. Available from: https://www.aifa.gov.it/documents/20142/1123276/Corticosteroidi_06.10.2020.pdf/075c9302- 895c-4d7e-11bc-0e2319082ffc
  48. EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation; 2020 [cited 2020 Oct 31]. Available from: https://www.ema.europa.eu/en/news/ema- endorses-use-dexamethasone-covid-19-patients-oxygen- mechanical-ventilation
  49. Arachchillage DRJ, Laffan M. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J ThrombHaemost. 2020;18(5):1233–1234. • This paper describes early evidences for the possible use of anticoagulants in the adjunctive therapy of COVID-19 patients.
  50. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J ThrombHaemost. 2020;18 (5):1094–1099.
  51. Low molecular weight heparin in adult patients with COVID-19; 2020 [cited 2020 Oct 31].
  52. WHO - Clinical management of COVID-19; [cited 31 Oct 2020]. Available from: https://www.who.int/publications/i/item/clinical- management-of-covid-19 • Updated version of the guidance document by WHO for clinicians caring COVID-19 patients during all phases of their disease.
  53. Neuberger A, Oraiopoulos N, Drakeman DL. Renovation as innovation: Isrepurposing the future of drug discovery research? Drug Discov Today. 2019;24(1):1-3. doi:https://doi.org/10.1016/j.drudis.2018.06.012.
  54. Gautret P, Lagier JC, Parola P, Meddeb L, Mailhe M, Doudier B, et al.Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of anopen-label non-randomized clinical trial. Int J Antimicrob Agents. 2020.doi:105949.
  55. Uyeki TM. Oseltamivir Treatment of Influenza in Children. Clin Infect Dis. 2018;66(10):1501
  56. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;Feb7:1–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32031570
  57. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-covid-198.

 

 

 

 

 

[Download PDF]
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy
Pharmaceutical Fields
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmaceutics
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Novel drug delivery system
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Nanotechnology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacology
Welcome to IJPBS,Pharmaceutics, Novel, drug, delivery, system, Nanotechnology, Pharmacology, Pharmacognosy Pharmacognosy
© Copyright 2009-2015 IJPBS, India. All rights reserved. Specialized online journals by ubijournal. Website by Ubitech Solutions
         Home I Contact I Terms & Conditions