A REVIEW ON THE ANTIPARASITIC DRUG IVERMECTIN FOR VARIOUS VIRAL INFECTIONS AND POSSIBILITIES OF USING IT FOR NOVEL SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2: NEW HOPE TO TREAT CORONAVIRUS DISEASE-2019

  • TALHA JABEEN Department of Pharmacy Practice, Bhaskar Pharmacy College, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
  • MOHD ABDUL KHADER Department of Pharmacy Practice, Bhaskar Pharmacy College, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
  • SHAYESTHA JABEEN Department of Pharmacy Practice, MRM College of Pharmacy, Jawaharlal Nehru Technological University, Bongloor, Telangana, India.

Abstract

The novel coronavirus infection has spread all over the world. With no specific drug or vaccine, the process of “drug repurposing” becomes a feasible solution. As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has 80% sequence similarity with the SARS-CoV, the nuclear import inhibitor “Ivermectin” (IVM) has recently been studied as a possible treatment option for coronavirus disease-2019 (COVID-19). The article aims to provide a review on structure and immunogenicity of SARS-CoV-2, indications of IVM for viral diseases, its possible mechanism on COVID-19 with a brief discussion on IVM structure, pharmacokinetics, adverse drug reactions, drug interactions, and contraindications. Further, we made possible comparisons of IVM with solidarity trial drugs and analyzed its major advantages, limitations and gave necessary recommendations for its use in future in vivo studies in the treatment of COVID-19.

Keywords: Severe acute respiratory syndrome coronavirus 2, Coronavirus disease-2019, Ivermectin, Drug repurposing, Solidarity trial

References

1. Lu H, Stratton CW, Tang Y. Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle. J Med Virol 2020;92:401-2.
2. Singhal T. A review of coronavirus disease-2019 (COVID-19). Indian J Pediatr 2020;87:281-6.
3. Ayoub MD. Carvedilol as a potential addition to the covid-19 therapeutic arsenal. Int J Pharm Pharm Sci 2020;12:87-9.
4. Zhou Y, Hou Y, Shen J, Huang Y. Network-based drug repurposing for novel coronavirus 2019 nCoV/SARS-CoV-2. Cell Discov 2020;6:14.
5. Hudu SA, Shinkafi SH, Umar S. An overview of recombinant vaccine technology, adjuvants and vaccine delivery methods. Int J Pharm Pharm Sci 2016;8:19-4.
6. Tayade MR, Shinkar DM, Patil PB, Saudagar RB. Emerging therapy for dengue. Int J Curr Pharm Sci 2018;10:1-4.
7. Yanuar A, Syahdi RR, Aryati WD. Parameter optimization and virtual screening Indonesian herbal database as human immunodeficiency virus-1 integrase inhibitor using autodock and vina. Int J App Pharm 2017;90:90-3.
8. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antivir Res 2020;178:104787.
9. Patel AN, David WG, Mandeep RM. Ivermectin in COVID-19 related critical illness. SSRN Electron J 2020; Available from: https://www. ssrn.com/abstract=3570270.
10. Ahmed SF, Quadeer AA, McKay MR. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses 2020;12:254.
11. Morse JS, Lalonde T, Xu S, Liu WR. Learning from the past: Possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. ChemBioChem 2020;21:730-8.
12. Prasad S, Cherian S, Abraham P. Transmission electron microscopy imaging of SARS-CoV-2. Indian J Med Res 2020;151:241-3.
13. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020;181:271-80.
14. Ashour DS. Ivermectin: From theory to clinical application. Int J Antimicrob Agents 2019;54:134-42.
15. Laing R, Gillan V, Devaney E. Ivermectin-old drug, new tricks? Trends Parasitol 2017;33:463-72.
16. Frieman M, Yount B, Heise M, Kopecky-Bromberg SA, Palese P, Baric RS. Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/golgi membrane. J Virol 2007;81:9812-24.
17. DailyMed-STROMECTOL-ivermectin tablet. Available from: http:// dailymed.nlm.nih.gov.
18. Tay MY, Fraser JE, Chan WK, Moreland NJ, Rathore AP, Wang C, et al. Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor ivermectin. Antivir Res 2013;99:301-6.
19. Lv C, Liu W, Wang B, Dang R, Qiu L, Ren J. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antivir Res 2018;159:55-62.
20. Lee YJ, Lee C. Ivermectin inhibits porcine reproductive and respiratory syndrome virus in cultured porcine alveolar macrophages. Arch Virol 2016;161:257-68.
21. Varghese FS, Kaukinen P, Gläsker S, Bespalov M, Hanski L, Wennerberg K, et al. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses. Antivir Res 2016;126:117-24.
22. Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin ?/?-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J 2012;443:851-6.
23. Azeem S, Ashraf M, Rasheed MA, Anjum AA, Hameed R. Evaluation of cytotoxicity and antiviral activity of ivermectin against Newcastle disease virus. Pak J Pharm Sci 2015;28:597-602.
24. Yang SN, Atkinson SC, Wang C, Lee A, Bogoyevitch MA, Borg NA, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin ?/?1 heterodimer. Antivir Res 2020;177:104760.
25. Raza S, Shahin F, Zhai W, Li H, Alvisi G, Yang K, et al. Ivermectin inhibits bovine herpesvirus 1 DNA polymerase nuclear import and interferes with viral replication. Microorganisms 2020;8:409.
26. Lundberg L, Pinkham C, Baer A, Amaya M, Narayanan A, Wagstaff KM. Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce venezuelan equine encephalitis virus replication. Antivir Res 2013;100:662-72.
27. Mastrangelo E, Pezzullo M, Burghgraeve TD, Kaptein S. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: New prospects for an old drug. J Antimicrob 2012;67:1884-94.
28. Gotz V, Magar L, Dornfeld D, Giese S. Influenza a viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Nature 2016;6:23138.
29. Rowland RR, Chauhan V, Fang Y, Pekosz A, Kerrigan M, Burton MD. Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: Absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells. J Virol 2005;79:11507-12.
30. Remme J, Baker RH, Sole GD, Dadzie KY. A community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. I. Effect on the microfilarial reservoir and the transmission of Onchocerca volvulus. Trop Med Parasitol 1989;40:367-74.
31. Sole GD, Remme J, Awadzi K, Accorsi S, Alley ES, Ba O, et al. Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: Combined results from eight community trials. Bull WHO 1989;67:707-20.
32. Pacqué M, Muñoz B, Poetscke G, Foose J, Taylor HR, Greene BM. Pregnancy outcome after inadvertent ivermectin treatment during community-based distribution. Lancet 1990;336:1486-9.
33. Canga AZ, Prietp AM. The pharmacokinetics and interactions of ivermectin in humans-a mini-review. AAPS J 2008;10:42-6.
34. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A. Compassionate use of remdesivir for patients with severe covid-19. N Engl J Med 2020;382:2327-36.
35. 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;57:279-83.
36. Human Prescription Drug Label. KALETRA-lopinavir and Ritonavir Tablet, Film Coated Kaletra-lopinavir and Ritonavir Solution. United States: AbbVie Inc. [Last accessed on 2019 Dec 26].
37. Abdolvahab MH, Mofrad MR, Schellekens H. Interferon beta: From molecular level to therapeutic effects. Int Rev Cell Mol Biol 2016;326:343-72.
38. Schmith VD. The approved dose of ivermectin alone is not the ideal dose for the treatment of COVID-19. Clin Pharmacol Ther 2020;2020:1889.
39. Gorial F. Efficacy of Ivermectin as Add on Therapy in COVID19 Patients: A Pilot Randomized Study. Report No: NCT04343092. Avaialable from:http://www.clinicaltrials.gov. [Last accessed on 2020 Jun 10].
40. Max Healthcare Insititute Limited. To Study the Effectiveness of Ivermectin With Standard of Care Treatment Versus Standard of Care Treatment for COVID 19 Cases. A Pilot Study. Report No: NCT04373824. Available from: http://www.clinicaltrials.gov. [Last accessed on 2020 May 10].
41. Okasha PD. Clinical Trial Evaluating Safety and Efficacy of Ivermectin and Nitazoxanide Combination as Adjuvant Therapy in COVID-19 Newly Diagnosed Egyptian Patients: A Tanta University Hope. Report No: NCT04360356. Available from: http://www.clinicaltrials.gov. [Last accessed on 2020 Apr 28].
42. Ivermectin Effect on SARS-CoV-2 Replication in Patients. Available from: http://www.COVID-19-fullTextView-ClinicalTrials.gov.
43. Sars-CoV-2/COVID-19 Ivermectin Navarra-ISGlobal. Available from: http://www.Trial-FullTextView-ClinicalTrials.gov.
44. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. A Phase II Trial to Promote Recovery From COVID-19 With Ivermectin or Endocrine Therapy. Report No: NCT04374279. Available from: http://www.clinicaltrials.gov. [Last accessed on 2020 May 10].
45. Abd-Elsalam S. Clinical Study Evaluating the Efficacy of Ivermectin and Nitazoxanide in COVID-19 Treatment. Report No: NCT04351347. Available from: http://www.clinicaltrials.gov. [Last accessed on 2020 Apr 28].
46. How a Grass Roots Health Movement Led to Acceptance of Ivermectin as a COVID-19 Therapy in Peru. Available from: http://www. trialsitenews.com.
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JABEEN, T., M. A. KHADER, and S. JABEEN. “A REVIEW ON THE ANTIPARASITIC DRUG IVERMECTIN FOR VARIOUS VIRAL INFECTIONS AND POSSIBILITIES OF USING IT FOR NOVEL SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2: NEW HOPE TO TREAT CORONAVIRUS DISEASE-2019”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 8, June 2020, pp. 21-27, doi:10.22159/ajpcr.2020.v13i8.38357.
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