Rational pharmacological approach to clinical studies for the treatment of SARS-COV-2 infection

Antônia Dailane dos Santos Rabêlo, Gizelle Gomes de Souza, Rosilene Ribeiro de Sousa, Charllyton Luis Sena da Costa

Resumo


Abstract

The global emergency generated by the COVID-19 pandemic caused by the SARS-COV-2 virus has created serious impacts on the different populations of the planet and has triggered the generation of scientific information on an unprecedented scale until then for a single topic. One of the consequences of the global scientific effort lies in the large number of substances already tested, by different methods, the search for an effective treatment for the infection and the consequent disease, remaining without absolute success so far. Assimilating the lessons, learned from the successful adoption of therapies combining multiple drugs used in HIV infection, the evidence obtained from the large amount of published information regarding the action of many substances with different mechanisms, now allows the proposition, in this work, of tests clinical trials for the evaluation of regimens composed of at least three drugs in combination. Rational combination schemes can target different molecular components of the virus affecting different points in the SARS-COV-2 replication cycle, such as virus fusion to the host cell, replication and viral particle assembly generating a potentially more effective synergistic effect than attempts using a single substance.

Keywords: antiviral, pandemic, combination therapy.


Texto completo:

HTML PDF inglês PDF português

Referências


World Health Organization. COVID-19 Global Research Roadmap: 2019 Novel coronavirus. Geneva, Switzerland: WHO; 2020.

Li H, Zhou Y, Zhang M, Wang H, Zhao Q, Liu J. Updated approaches against SARS-CoV-2. Antimicrob Agents Chemother 2020;64(6):e00483-20. https://doi.org/doi.org/10.1128/AAC.00483-20

Hussain S, Xie YJ, Li D, Malik SI, Hou JC, Leung EL et al. Current strategies against COVID-19. Chinese Medicine 2020;15(70). https://doi.org/10.1186/s13020-020-00353-7

Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov 2020;19(3):149-50. https://doi.org/10.1038/d41573-020-00016-0

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G et al. A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. New Engl J Med 2020;382(19):1787-99. https://doi.org/10.1056/NEJMoa2001282

Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L 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. https://doi.org/10.1016/j.medmal.2020.03.006

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. https://doi.org/10.1016/j.antiviral.2020.104787

Lotfi M, Hamblin MR, Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020;508:254-66. https://doi.org/10.1016/j.cca.2020.05.044

Maenza J, Flexner C. Combination antiretroviral therapy for HIV infection [published correction appears in Am Fam Physician 1998;58(5):1084. Am Fam Physician 1998;57(11):2789-98.

Eggleton JS, Nagalli S. Highly Active Antiretroviral Therapy (HAART) [Updated 2020 Jul 5]. Treasure Island FL: StatPearls; 2020.

Wensing AM, van Maarseveen NM, Nijhuis M. Fifteen years of HIV Protease Inhibitors: raising the barrier to resistance. Antiviral Res 2010;85(1):59-74. https://doi.org/10.1016/j.antiviral.2009.10.003

Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res 2010;85(1):1-18. https://doi.org/10.1016/j.antiviral.2009.10.002

Lv Z, Chu Y, Wang Y. HIV protease inhibitors: a review of molecular selectivity and toxicity. HIV AIDS (Auckl) 2015;7:95-104. https://doi.org/10.2147/HIV.S79956

Powderly WG. Integrase inhibitors in the treatment of HIV-1 infection. J Antimicrob Chemother 2010;65(12):2485-8. https://doi.org/10.1093/jac/dkq350

Penazzato M, Giaquinto C. Role of non-nucleoside reverse transcriptase inhibitors in treating HIV-infected children. Drugs 2011;71(16):2131-49. https://doi.org/10.2165/11597680-000000000-00000

Moran CA, Weitzmann MN, Ofotokun I. The protease inhibitors and HIV-associated bone loss. Curr Opin HIV AIDS 2016;11(3):333-42. https://doi.org/10.1097/COH.0000000000000260

World Health Organization. Updated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection - December 2018. Geneva: WHO; 2018.

Maeda K, Das D, Kobayakawa T, Tamamura H, Takeuchi H. Discovery and Development of anti-HIV therapeutic agents: progress towards improved HIV medication. Curr Top Med Chem 2019;19(18):1621-49. https://doi.org/10.2174/1568026619666190712204603

Chaudhuri S, Symons JA, Deval J. Innovation and trends in the development and approval of antiviral medicines: 1987-2017 and beyond. Antiviral Res 2018;155:76-88. https://doi.org/10.1016/j.antiviral.2018.05.005

Himmel DM, Arnold E. Non-nucleoside reverse transcriptase inhibitors join forces with integrase inhibitors to combat HIV. Pharmaceuticals (Basel) 2020;13(6):122. https://doi.org/10.3390/ph13060122

Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 2020;395(10238):1695-1704. https://doi.org/10.1016/S0140-6736(20)31042-4

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395(10236):1569-78. https://doi.org/10.1016/S0140-6736(20)31022-9

Antinori S, Cossu MV, Ridolfo AL, Rech R, Bonazzetti C, Pagani G et al. Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status. Pharmacol Res 2020;158:104899. https://doi.org/10.1016/j.phrs.2020.104899

Cao Y, Wei J, Zou L, Jiang T, Wang G, Chen L et al. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial. J Allergy Clin Immunol 2020;146(1):137-46.e3. https://doi.org/10.1016/j.jaci.2020.05.019

Coenen S, van der Velden AW, Cianci D, Goossens H, Bongard E, Saville BR et al. (2020). Oseltamivir for coronavirus illness: post-hoc exploratory analysis of an open-label, pragmatic, randomised controlled trial in European primary care from 2016 to 2018. BR J Gen Pract 2020;70(696):e444–e9. https://doi.org/10.3399/bjgp20X711941

Lu CC, Chen MY, Lee WS, Chang YL. Potential therapeutic agents against COVID-19: What we know so far. J Chin Med Assoc 2020;83(6):534-6. https://doi.org/10.1097/JCMA.0000000000000318

Park SJ, Yu KM, Kim YI, Kim SM, Kim EH, Kim SG et al. Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 Infection in Ferrets. mBio, 2020;11(3):e01114-20. https://doi.org/10.1128/mBio.01114-20

Yamaya M, Nishimura H, Deng X, Kikuchi A, Nagatomi R. Protease inhibitors: candidate drugs to inhibit severe acute respiratory syndrome coronavirus 2 replication. Tohoku J Exp Med 2020;251(1):27-30. https://doi.org/10.1620/tjem.251.27

McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res 2020;157:104859. https://doi.org/10.1016/j.phrs.2020.104859

Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A et al. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet 2020;395(10223):e30–e31. https://doi.org/10.1016/S0140-6736(20)30304-4

Zhou H, Fang Y, Xu T, Ni WJ, Shen AZ, Meng XM. Potential therapeutic targets and promising drugs for combating SARS-CoV-2. Br J Pharmacol 2020;177(14):3147-61. https://doi.org/10.1111/bph.15092

Boriskin YS, Pécheur EI, Polyak SJ. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection. Virol J 2006;3:56. https://doi.org/10.1186/1743-422X-3-56

Huang D, Yu H, Wang T, Yang H, Yao R, Liang Z. Efficacy and safety of umifenovir for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis ahead of print 2020 Jul 3. J Med Virol 2020;10. https://doi.org/10.1002/jmv.26256

Beck BR, Shin B, Choi Y, Park S, Kang K. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J 2020;18:784-90. https://doi.org/10.1016/j.csbj.2020.03.025




DOI: http://dx.doi.org/10.33233/eb.v19i4.4349

Apontamentos

  • Não há apontamentos.