An Examination of Ivermectin's Antiviral Properties and Their Application in the Management of Coronavirus Disease in 2019
Keywords:
Ivermectin, COVID-19, SARS-CoV-2, Clinical trials, AntiviralAbstract
Background
The coronavirus disease-2019 (COVID-19) originated in China and was declared a pandemic by the World Health Organization (WHO) on 11th March 2020. Since its emergence in December 2019, there have been challenges in developing drugs that are effective against the virus. Currently, COVID-19 is managed using symptomatic and supportive therapies, antiviral agents, cellular and immunotherapy. Besides, most of the treatment modalities are still under investigation and treatment guidelines vary from one country to another. Ivermectin is among the drugs that are being used as part of treatment guidelines in certain countries like the Republic of Peru. However, the WHO recommends that ivermectin only be used in clinical trials.
Aim
The authors conducted this review to explore published studies on the possible therapeutic effects of ivermectin against active infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a causative agent of COVID-19.
Methods
A literature search was conducted using Google Scholar, PubMed and EMBASE for articles published from 2016 to 2021. Search words used included ivermectin, antiviral, COVID-19, efficacy, safety, dosing, lower mortality rate, hospitalised patients and the Boolean operator ‘AND’.
Results
A few clinical trials have shown that ivermectin is safe for use in humans at specific doses and reduces the severity of the infection. Ivermectin was seen to reduce the signs and symptoms associated with COVID-19 in some studies while others showed no significant reduction. However, more studies must be conducted to ascertain its use in treating COVID-19.
Conclusion
Since many clinical trials are being conducted on the use of ivermectin to treat COVID-19, full evidence will be used to support its use in humans. Currently, some countries that are using ivermectin for treating COVID-19 have reported it to be effective and reduces morbidity and mortality associated with the disease. Therefore, countries should collaborate and provide full evidence for the use of ivermectin in humans to manage COVID-19.
References
World Health Organization (WHO). Pneumonia of unknown cause—China. 2020. Web site. who int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/. Accessed April. 1, 2020.
Zhao S, Lin Q, Ran J, Musa SS, Yang G, Wang W, et al. Prelimi-nary estimation of the basic reproduction number of novel coro-navirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak. Int J Infect Dis. 2020; 92: 214-217. doi: 10.1016/j.ijid.2020.01.050
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical fea-tures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497-506. doi: 10.1016/S0140- 6736(20)30183-5
Zhao D, Yao F, Wang L, Zheng L, Gao Y, Ye J, et al. A com-parative study on the clinical features of coronavirus 2019 (CO-VID-19) pneumonia with other pneumonias. Clin Infect Dis. 2020; 71(15): 756-761. doi: 10.1093/cid/ciaa247
Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed. 2020; 91(1): 157-160. doi: 10.23750/abm.v91i1.9397
Zanke AA, Thenge RR, Adhao VS. COVID-19: A pandemic de-clare by world health organization. IP International Journal of Compre-hensive and Advanced Pharmacology. 2020; 5(2): 49-57. doi: 10.18231/j. ijcaap.2020.012
McIntosh K, Hirsch MS, Bloom A. Coronavirus disease 2019 (COVID-19). UpToDate Hirsch MS Bloom. 2020; 5(1).
Mudenda S. Letter to editor: Coronavirus disease (COVID-19): A global health problem. International Journal of Pharmaceutics & Pharmacology. 2020; 4(1): 1-2. doi: 10.31531/2581-3080.1000141
Alimohamadi Y, Sepandi M, Taghdir M, Hosamirudsari H. De-termine the most common clinical symptoms in COVID-19 pa-tients: As systematic review and meta-analysis. J Prev Med Hyg. 2020; 61(3): E304-E312. doi: 10.15167/2421-4248/jpmh2020.61.3.1530
Larsen JR, Martin MR, Martin JD, Kuhn P, Hicks JB. Modeling the onset of symptoms of COVID-19. Front Public Health. 2020; 8: 473. doi: 10.3389/fpubh.2020.00473
Rothan HA, Byrareddy SN. The epidemiology and pathogen-esis of coronavirus disease (COVID-19) outbreak. J Autoimmun. 2020; 109: 102433. doi: 10.1016/j.jaut.2020.102433
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical char-acteristics of 138 hospitalized patients with 2019 novel coronavi-rus–infected pneumonia in Wuhan, China. JAMA. 2020; 323(11): 1061-1069. doi: 10.1001/jama.2020.1585
Pullen MF, Skipper CP, Hullsiek KH, Bangdiwala AS, Pastick KA, Okafor EC, et al. Symptoms of COVID-19 outpatients in the United States. Open Forum Infect Dis. 2020; 7(7): ofaa271. doi: 10.1093/ofid/ofaa271 Hikaambo CN et al
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 α/β1 heterodimer. Antiviral Res. 2020; 177: 104760. doi: 10.1016/j.antiviral.2020.104760
Jans DA, Martin AJ, Wagstaff KM. Inhibitors of nuclear transport. Curr Opin Cell Biol. 2019; 58: 50-60. doi: 10.1016/j. ceb.2019.01.001
Pott-Junior H, Paoliello MMB, Miguel AdQC, da Cunha AF, de Melo Freire CC, Neves FF, et al. Use of ivermectin in the treat-ment of Covid-19: A pilot trial. Toxicol Rep. 2021; 8: 505-510. doi: 10.1016/j.toxrep.2021.03.003
Jans DA, Wagstaff KM. Ivermectin as a broad-spectrum host-directed antiviral: The real deal? Cells. 2020; 9(9): 2100. doi: 10.3390/cells9092100
Espitia-Hernandez G, Munguia L, Diaz-Chiguer D, Lopez-Elizalde R, Jimenez-Ponce F. Effects of ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study. Biomedical Research. 2020; 31(5): 129-133.
Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci. 2020; 50(SI-1): 611-619. doi: 10.3906/sag-2004-145
Sharun K, Dhama K, Patel SK, Pathak M, Tiwari R, Singh BR, et al. Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19. Ann Clin Microbiol Antimicrob. 2020; 19(1): 23. doi: 10.1186/s12941-020-00368-w
Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. Ivermectin: An award-winning drug with ex-pected antiviral activity against COVID-19. J Control Release. 2021; 329: 758-761. doi: 10.1016/j.jconrel.2020.10.009
Panel C-TG. Coronavirus disease 2019 (COVID-19) treatment guidelines. National Institutes of Health. 2020.
Heidary F, Gharebaghi R. Ivermectin: A systematic review from antiviral effects to COVID-19 complementary regimen. The Journal of Antibiotics. 2020; 73(9): 1-10. doi: 10.1038/s41429-020-0336-z
Kaur H, Shekhar N, Sharma S, Sarma P, Prakash A, Medhi B. Ivermectin as a potential drug for treatment of COVID-19: An in-sync review with clinical and computational attributes. Pharmacol Rep. 2021; 73(3): 736-749. doi: 10.1007/s43440-020-00195-y
Lv C, Liu W, Wang B, Dang R, Qiu L, Ren J, et al. Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo. Antiviral Res. 2018; 159: 55-62. doi: 10.1016/j.antiviral.2018.09.010
Krolewiecki A, Lifschitz A, Moragas M, Travacio M, Valentini R, Alonso DF, et al. Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial. EClini-calMedicine. 2021; 37: 100959. doi: 10.1016/j.eclinm.2021.100959
Rajter JC, Sherman MS, Fatteh N, Vogel F, Sacks J, Rajter J-J. Use of ivermectin is associated with lower mortality in hospitalized patients with coronavirus disease 2019: The ivermectin in COVID nineteen study. Chest Journal. 2021; 159(1): 85-92. doi: 10.1016/j. chest.2020.10.009
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; 178: 104787. doi: 10.1016/j. antiviral.2020.104787
López-Medina E, López P, Hurtado IC, Dávalos DM, Ramirez O, Martínez E, et al. Effect of ivermectin on time to resolution of symptoms among adults with mild COVID-19: A random-ized clinical trial. JAMA. 2021; 325(14): 1426-1435. doi: 10.1001/ jama.2021.3071
Momekov G, Momekova D. Ivermectin as a potential COV-ID-19 treatment from the pharmacokinetic point of view: Anti-viral levels are not likely attainable with known dosing regimens. Biotechnology & Biotechnological Equipment. 2020; 34(1): 469-474. doi: 10.1080/13102818.2020.1775118
Kinobe RT, Owens L. A systematic review of experimental evi-dence for antiviral effects of ivermectin and an in silico analysis of ivermectin’s possible mode of action against SARS-CoV-2. Fundam Clin Pharmacol. 2021; 35(2): 260-276. doi: 10.1111/fcp.12644
Schmith VD, Zhou J, Lohmer LR. The approved dose of iver-mectin alone is not the ideal dose for the treatment of COVID-19. Clin Pharmacol Ther. 2020; 108(4): 762-765. doi: 10.1002/cpt.1889
Croci R, Bottaro E, Chan KWK, Watanabe S, Pezzullo M, Mastrangelo E, et al. Liposomal systems as nanocarriers for the antiviral agent ivermectin. Int J Biomater. 2016; 2016: 8043983. doi: 10.1155/2016/8043983 Submit your article to this journal | https://openventio.org/submit-manuscript/
Bittencourt SC, Caponi S, Maluf S. Pharmacology in the twentieth century: The science of drugs through the analysis of Goodman and Gilman’s textbook. Hist Cienc Saude Manguinhos. 2013;20(2):499-520. doi: 10.1590/S0104-59702013005000007
Camprubí D, Almuedo-Riera A, Martí-Soler H, Soriano A, Hurtado JC, Subirà C, et al. Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients. PLoS One. 2020; 15(11): e0242184. doi: 10.1371/journal.pone.0242184
World Health Organization (WHO). Therapeutics and CO-VID-19: Living guideline. 2021. Web site. https://www.who.int/ publications/i/item/WHO-2019-nCoV-therapeutics-2021.3. Ac-cessed April 1, 2020.
Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, et al. A five-day course of ivermectin for the treat-ment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 2021; 103: 214-216. doi: 10.1016/j.ijid.2020.11.191
Kim MS, An MH, Kim WJ, Hwang T-H. Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis. PLoS Med. 2020; 17(12): e1003501. doi: 10.1371/journal.pmed.1003501
Vallejos J, Zoni R, Bangher M, Villamandos S, Bobadilla A, Plano F, et al. Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial. BMC Infect Dis. 2021; 21(1): 635. doi: 10.1186/s12879-021-06348-5
Abd-Elsalam S, Noor RA, Badawi R, Khalaf M, Esmail ES, So-liman S, et al. Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study. J Med Virol. 2021; 93(10): 5833-5838. doi: 10.1002/jmv.27122
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