NCT
HOME CURRENT ARCHIVE COVID-19
HOME CURRENT ARCHIVE PUBLISH INSTRUCTIONS
FOR AUTHORS COVID-19 LOG IN / REGISTER HISTORY ABOUT US DIRECTORY CONTACT
Repositioning drugs and specific drugs in preclinical phase for COVID-19

Cabrera-Sánchez, Carlos Francisco1; Sánchez-Godínez, J. Yureri2,3; González, Yolanda3





2021, Number 4

2021; 80 (4)






ABSTRACT

Drug repositioning is an activity commonly performed by laboratories, and consists of the commercial use of a drug for a different purpose for which it was investigated or approved. In 2009, the COVID-19 pandemic began, caused by a new virus, SARS-CoV-2, a virus for which the human population has no immunity, and for which there is no effective treatment. As a first strategy to treat severely ill patients, drugs were repositioned for emergency use if they were shown to be at least theoretically effective against SARS-CoV-2. Once the results of the clinical studies were available, their effectiveness in preventing severe and/or fatal cases was evaluated. If the drug showed significant effectiveness, the World Health Organization (WHO) issued a recommendation for its use, otherwise a warning was issued to discontinue its use for COVID-19. This review describes the drugs that have been repositioned following this process, as well as the new SARS-CoV-2 specific drugs that are in experimental and preclinical phases.

KEYWORDS

Drug repositioning, emergency use, COVID-19, SARS-CoV-2.

REFERENCES

  1. Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res [Internet]. 2018;8(2):317-331. Available in: http://www.ncbi.nlm.nih.gov/pubmed/29511601%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC5835698

  2. Dominguez-Gomez G, Chavez-Blanco A, Medina-Franco JL, Saldivar-Gonzalez F, Flores-Torrontegui Y, Juarez M, et al. Ivermectin as an inhibitor of cancer stem-like cells. Mol Med Rep. 2018;17(2):3397-3403.

  3. OMS. Manejo clínico de la COVID-19. Organización Mundial de la Salud [Internet]. 2020;(5):1-68. Available in: https://apps.who.int/iris/bitstream/handle/10665/332638/WHO-2019-nCoV-clinical-2020.5-spa.pdf

  4. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell, E, Fan E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA [Internet]. 2012;307(23):2526-2533. Available in: https://doi.org/10.1001/jama.2012.5669

  5. De DESDELAC, Subsecretar X, Prestaci DE, Servicios DE, Direcci I, Medicamentos DE. Guía Farmacoterapéutica de Medicamentos empleados en el tratamiento de pacientes con enfermedad COVID-19. 2020.

  6. Wang MY, Zhao R, Gao LJ, Gao XF, Wang DP, Cao JM. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol. 2020;10:587269.

  7. Bartoli A, Gabrielli F, Alicandro T, Nascimbeni F, Andreone P. COVID-19 treatment options: a difficult journey between failed attempts and experimental drugs. Intern Emerg Med [Internet]. 2021;16(2):281-308. Available in: https://doi.org/10.1007/s11739-020-02569-9

  8. Mohamadian M, Chiti H, Shoghli A, Biglari S, Parsamanesh N, Esmaeilzadeh A. COVID-19: virology, biology and novel laboratory diagnosis. J Gene Med. 2021;23(2):e3303.

  9. Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J Microbiol Immunol Infect [Internet]. 2021;54(2):159-163. Available in: https://doi.org/10.1016/j.jmii.2020.03.022

  10. Samudrala PK, Kumar P, Choudhary K, Thakur N, Wadekar GS, Dayaramani R, et al. Virology, pathogenesis, diagnosis and in-line treatment of COVID-19. Eur J Pharmacol. 2020;883:173375.

  11. Magro G. SARS-CoV-2 and COVID-19: What are our options? Where should we focus our attention on to find new drugs and strategies? Travel Med Infect Dis. 2020;37:101685.

  12. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. 2021.

  13. SSA. Uso de plasma convaleciente para atención de pacientes con COVID-19. 2020;2(195).

  14. Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med. 2021;384(3):238-251.

  15. Wang Y, Zhang L, Sang L, Ye F, Ruan S, Zhong B, et al. Kinetics of viral load and antibody response in relation to COVID-19 severity. J Clin Invest. 2020;130(10):5235-5244.

  16. Dougan M, Nirula A, Gottlieb RL, Azizad M, Mocherla B, Chen P, et al. Bamlanivimab+etesevimab for treatment of COVID-19 in high-risk ambulatory patients. [Internet]. 2021. Available in: https://www.croiconference.org/wp-content/uploads/sites/2/ resources/2021/vCROI-2021-Abstract-eBook.pdf

  17. Federal Drug Administration. Fact Sheet for Health Care Providers. 2020;1-36. Available in: https://pi.lilly.com/eua/bamlanivimab-eua-factsheet-hcp.pdf

  18. FDA. Emergency use authorization (EUA) of casirivimab and imdevimab. 2019;1-36.

  19. Phase 3 trial shows REGEN-COV (casirivimab with imdevimab) antibody cocktail reduced hospitalization or death by 70% in non-hospitalized COVID-19 patients. [Internet]. 2021. Available in: https://investor.regeneron.com/news-releases/news-release-details/phase-3-trialshows-regen-covtm-casirivimab-imdevimab-antibody

  20. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.

  21. Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med. 2018;197(6):757-767.

  22. Lansbury L, Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam J, Lim WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database Syst Rev. 2019;2(2):CD010406.

  23. Recomendaciones para el tratamiento de la infección por SARS-CoV-2, agente causal de COVID-19. Harefuah. 2020;102(1):40-41.

  24. 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):137-146.e3. Available in: https://www.ncbi.nlm.nih.gov/pubmed/32470486

  25. Ovilla-Martínez R, De la Peña-Celaya JA, Báez-Islas PE, Del Bosque-Patoni C, Guzmán-Bouilloud NE, Rodríguez-Sandoval R, et al. Tratamiento exitoso con ruxolitinib en un caso de neumonía por SARS-CoV-2 en México. Med Int Mex [Internet]. 2020;36(5):740-744. Available in: https://doi.org/10.24245/mim. V36i5.4372

  26. Migita K, Izumi Y, Jiuchi Y, Kozuru H, Kawahara C, Izumi M, et al. Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis. Clin Exp Immunol. 2014;175(2):208-214.

  27. Salgado LA. Pfizer avanza en la batalla contra el COVID-19 en múltiples frentes. Codigo F [Internet]. 2020. Available: https://codigof.mx/pfizer-avanza-en-la-batalla-contra-el-covid-19-en-multiples-frentes/

  28. Rodríguez A. AstraZeneca sube inversión en México [Internet]. 2020. Available in: https://www.elfinanciero.com.mx/empresas/astrazeneca-sube-inversion-en-mexico/

  29. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271.

  30. Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. Nature. 2020;585(7824):273-276. doi: 10.1038/s41586-020-2423-5.

  31. Garrod M. La Cofepris autoriza el uso de emergencia del remdesivir en México. [Internet]. 2021. Available in: https://codigof.mx/la-cofepris-autoriza-el-uso-de-emergencia-del-remdesivir-en-mexico/

  32. Delang L, Abdelnabi R, Neyts J. Favipiravir as a potential countermeasure against neglected and emerging RNA viruses. Antiviral Res [Internet]. 2018;153:85–94. Available in: https://doi.org/10.1016/j.antiviral.2018.03.003

  33. Furuta Y, Komeno T, Nakamura T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci [Internet]. 2017;93(7):449-463. Available in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713175/pdf/pjab-93-449

  34. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60.

  35. Krishna G, Pillai VS, Veettil MV. Approaches and advances in the development of potential therapeutic targets and antiviral agents for the management of SARS-CoV-2 infection. 2020; 885, 173450. Available in: https://doi.org/10.1016/j.ejphar.2020.173450

  36. Ryu YB, Park SJ, Kim YM, Lee JY, Seo WD, Chang JS, et al. SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii. Bioorganic Med Chem Lett. 2010;20(6):1873-1876. Available from: https://doi.org/10.1016/j.bmcl.2010.01.152

  37. Asai A, Konno M, Ozaki M, Otsuka C, Vecchione A, Arai T, et al. COVID-19 drug discovery using intensive approaches. Int J Mol Sci. 2020;21(8):2839. Available in: https://doi.org/10.3390/ijms21082839

  38. Li F, Han M, Dai P, Xu W, He J, Tao X, et al. Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide. Nat Commun. 2021;12(1). Available from:https://doi.org/10.1038/s41467-021-21171-x

  39. Rosenke K, Hansen F, Schwarz B, Feldmann F, Haddock E, Rosenke R, et al. Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model. Nat Commun. 2021;12(1). Available from: https://doi.org/10.1038/s41467-021-22580-8

  40. Cox RM, Wolf JD, Plemper RK. Therapeutic MK-4482/EIDD-2801 Blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol. 2021;6:11-18. Available in: https://doi.org/10.1038/s41564-020-00835-2


2021, Number 4

2021; 80 (4)