Main Article Content

Authors

The coronavirus disease 2019 (COVID-19) was declared as pandemic on March 2020 by the World Health Organization. This respiratory disease is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and current efforts are focused in finding pharmaceutical alternatives and vaccines for both, preventing and treating the infected patients around the world. After quarantine and lockdown periods, the treatment of the disease is still limited to symptomatology management and remission to critical care units of the most severe cases. America accumulate the highest number of cases and casualties and the increased pressure over the economy led to the relaxing of mitigation measures. Several clinical trials involving antivirals have been conducted as available alternatives on the short term to face the increasing rate of contagions while experimental vaccines are properly developed and tested. Scientific literature refers a set of FDA approved drugs as repurposed compounds with potential action on the viral mechanism of SARS-CoV-2. In Colombia some of those substances are currently commercialized as antivirals and antiparasitic over-the-counter drugs, while other drugs also in the panorama are unavailable but potentially accessible in the short term for treating the COVID-19 in Colombia, until a massive vaccination campaign can be deployed in the country.

1.
Gómez Ríos DA, López-Agudelo VA, Urrego-Sepúlveda JC, Ramirez-Malule HD. Research on repurposed antivirals currently available in Colombia as treatment alternatives for COVID-19. inycomp [Internet]. 2021 Jan. 15 [cited 2024 Nov. 5];23(1):e10290. Available from: https://revistaingenieria.univalle.edu.co/index.php/ingenieria_y_competitividad/article/view/10290

Walls AC, Park Y-J, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell [Internet]. 2020 Apr;181(2):281-292.e6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0092867420302622

Gómez-Ríos D, López-Agudelo VA, Ramírez-Malule H. Repurposing antivirals as potential treatments for SARS-CoV-2: From SARS to COVID-19. J Appl Pharm Sci [Internet]. 2020 May 8;10(5):1–9. Available from: https://japsonline.com/abstract.php?article_id=3133&sts=2

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med [Internet]. 2020 Apr 30;382(18):1708–20. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2002032

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet [Internet]. 2020;395(10229):1054–62. Available from: http://dx.doi.org/10.1016/S0140-6736(20)30566-3

Del Toro Rubio M, Díaz Pérez A, Barrios Puerta Z, Castillo Avila IY. Automedicación y creencias en torno a su práctica en Cartagena, Colombia. Rev Cuid [Internet]. 2017 Jan 1;8(1):1509. Available from: http://www.revistacuidarte.org/index.php/cuidarte/article/download/367/759

Tobón Marulanda FÁ, Montoya Pavas S, Orrego Rodriguez MÁ. Automedicación familiar, un problema de salud pública. Educ Médica [Internet]. 2018 Oct;19:122–7. Available from: http://dx.doi.org/10.1016/j.edumed.2017.03.004

López JJ, Dennis R, Moscoso SM. Estudio sobre la Automedicación en una Localidad de Bogotá. Rev Salud Pública [Internet]. 2009 Jun;11(3):432–42. Available from: http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0124-00642009000300012&lng=es&nrm=iso&tlng=es

Hu Z, Ge Q, Li S, Boerwincle E, Jin L, Xiong M. Forecasting and evaluating intervention of Covid-19 in the World. ArXiV [Internet]. 2020 Mar 21; Available from: http://arxiv.org/abs/2003.09800

Freeman AM, Leigh TR. Viral pneumonia [Internet]. StatPearls. 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513286/

Chinese Centre for Disease Control and Prevention. Diagnosis and treatment [Internet]. COVID-19 Prevention and Control. Beijing; 2020. Available from: http://www.chinadaily.com.cn/specials/diagnosisandtreatment-Asia.pdf

Saavedra Trujillo CH. Resumen: Consenso colombiano de atención, diagnóstico y manejo de la infección por SARS-COV-2/COVID-19 en establecimientos de atención de la salud - Recomendaciones basadas en consenso de expertos e informadas en la evidencia. Infectio [Internet]. 2020 Mar 26;24(3). Available from: http://www.revistainfectio.org/index.php/infectio/article/view/852

Ramírez-Malule H, López-Agudelo VA, Gómez-Ríos D. Candida auris: a bibliometric analysis of the first ten years of research (2009–2018). J Appl Pharm Sci [Internet]. 2020 Mar;10(3):12–21. Available from: https://japsonline.com/abstract.php?article_id=3084&sts=2

Gómez-Ríos D, Ramírez-Malule H. Bibliometric analysis of recent research on multidrug and antibiotics resistance (2017–2018). J Appl Pharm Sci. 2019 May;9(5):112–6.

Ramirez-Malule H. Bibliometric Analysis of Global Research on Clavulanic Acid. Antibiotics [Internet]. 2018 Nov 26;7(4):102. Available from: http://www.mdpi.com/2079-6382/7/4/102

van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84(2):523–38.

Chen Q, Allot A, Lu Z. Keep up with the latest coronavirus research. Nature. 2020;579(7798):193.

Gómez-Ríos D, Ramirez-Malule D, Ramirez-Malule H. The effect of uncontrolled travelers and social distancing on the spread of novel coronavirus disease (COVID-19) in Colombia. Travel Med Infect Dis [Internet]. 2020 May;35(April):101699. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1477893920301678

Migración Colombia. Flujos Migratorios de Colombianos y Extranjeros [Internet]. 2020. Available from: https://public.tableau.com/profile/migraci.n.colombia#!/vizhome/FlujosMigratorios-2020/FlujosMigratoriosdeColombianos2017

Ramírez-malule H, Ramirez-malule D, Gómez-ríos D. Mitigating the COVID-19 spread : a challenge and an opportunity Mitigar la propagación de la COVID-19 : un desafío y una oportunidad. Ing Y Compet [Internet]. 2020 May 26;22(2):1–4. Available from: http://revistaingenieria.univalle.edu.co/index.php/ingenieria_y_competitividad/article/view/9491

Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents [Internet]. 2020 Mar;105949. Available from: https://doi.org/10.1016/j.ijantimicag.2020.105949

Rolain JM, Colson P, Raoult D. Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century. Int J Antimicrob Agents. 2007;30(4):297–308.

Mehra MR, Desai SS, Ruschitzka F, Patel AN. Articles Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet [Internet]. 2020;6736(20):1–10. Available from: http://dx.doi.org/10.1016/S0140-6736(20)31180-6

Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: An old drug against today’s diseases? Lancet Infect Dis. 2003;3(11):722–7.

Blau DM, Holmes K V. Human Coronavirus HCoV-229E Enters Susceptible Cells via the Endocytic Pathway. In: Advances in Experimental Medicine and Biology [Internet]. Springer Berlin Heidelberg; 2001. p. 193–8. Available from: http://link.springer.com/10.1007/978-1-4615-1325-4_31

Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:1–10.

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):269–71.

Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis [Internet]. 2020 Mar 9;2:1–25. Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa237/5801998

Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov [Internet]. 2020;6(1):16. Available from: http://www.nature.com/articles/s41421-020-0156-0

Chang R, Sun W-Z. Repositioning Chloroquine as Ideal Antiviral Prophylactic against COVID-19 - Time is Now. Preprints. 2020;(March):1–26.

Chandwani A, Shuter J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther Clin Risk Manag. 2008;4(5):1023.

Konvalinka J, Kräusslich HG, Müller B. Retroviral proteases and their roles in virion maturation. Virology. 2015;479–480:403–17.

Chan JFW, Chan KH, Kao RYT, To KKW, Zheng BJ, Li CPY, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect [Internet]. 2013;67(6):606–16. Available from: http://dx.doi.org/10.1016/j.jinf.2013.09.029

Park SY, Lee JS, Son JS, Ko JH, Peck KR, Jung Y, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect. 2019;101(1):42–6.

Arabi YM, Asiri AY, Assiri AM, Aziz Jokhdar HA, Alothman A, Balkhy HH, et al. Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial. Trials. 2020;21(1):8.

Arabi YM, Alothman A, Balkhy HH, Al-Dawood A, AlJohani S, Al Harbi S, et al. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): Study protocol for a randomized controlled trial. Trials. 2018;19(1):1–13.

Bhatnagar T, Murhekar M, Soneja M, Gupta N, Giri S, Wig N, et al. Lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease 2019 patients in India: Protocol for restricted public health emergency use. Indian J Med Res [Internet]. 2020;76(11):1532–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23144490

Huang Y, Tu M, Wang S, Chen S, Zhou W, Chen D, et al. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. Travel Med Infect Dis [Internet]. 2020;(February):101606. Available from: https://doi.org/10.1016/j.tmaid.2020.101606

Liu F, Xu A, Zhang Y, Xuan W, Yan T, Pan K, et al. Patients of COVID-19 may benefit from sustained lopinavir-combined regimen and the increase of eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis [Internet]. 2020; Available from: https://doi.org/10.1016/j.ijid.2020.03.013

Yan D, Liu X, Zhu Y, Huang L, Zhang G, Gao Y, et al. Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in patients with SARS-CoV-2 infection. medRxiv [Internet]. 2020 Jan 1;2020.03.22.20040832. Available from: http://medrxiv.org/content/early/2020/03/30/2020.03.22.20040832.abstract

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. N Engl J Med [Internet]. 2020;1–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32187464

Yao T, Qian J, Zhu W, Wang Y, Wang G. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option. J Med Virol. 2020;(February):1–8.

Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396).

Brown AJ, Won JJ, Graham RL, Dinnon KH, Sims AC, Feng JY, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res [Internet]. 2019;169(June):104541. Available from: https://doi.org/10.1016/j.antiviral.2019.104541

Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun [Internet]. 2020;11(1). Available from: http://dx.doi.org/10.1038/s41467-019-13940-6

de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci. 2020;117(12):201922083.

Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for the Treatment of Covid-19 — Preliminary Report. N Engl J Med [Internet]. 2020 May 22;NEJMoa2007764. Available from: http://www.nejm.org/doi/10.1056/NEJMoa2007764

Chaccour C, Hammann F, Ramón-García S, Rabinovich NR. Ivermectin and COVID-19: Keeping rigor in times of urgency. Am J Trop Med Hyg. 2020;102(6):1156–7.

Hossen MS, Barek MA, Jahan N, Safiqul Islam M. A Review on Current Repurposing Drugs for the Treatment of COVID-19: Reality and Challenges. SN Compr Clin Med [Internet]. 2020;1–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32904710%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC7457893

Schmith VD, Zhou J, Lohmer LRL. The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID-19. Clin Pharmacol Ther. 2020;0(0):1–4.

Ivashkiv LB, Donlin LT. Regulation of type i interferon responses. Nat Rev Immunol. 2014;14(1):36–49.

McNab F, Mayer-Barber K, Sher A, Wack A, O’Garra A. Type I interferons in infectious disease. Nat Rev Immunol. 2015;15(2):87–103.

Ströher U, DiCaro A, Li Y, Strong JE, Aoki F, Plummer F, et al. Severe Acute Respiratory Syndrome–Related Coronavirus Is Inhibited by Interferon‐α. J Infect Dis. 2004;189(7):1164–7.

Tan ELC, Ooi EE, Lin CY, Tan HC, Ling AE, Lim B, et al. Inhibition of SARS Coronavirus Infection in Vitro with Clinically Approved Antiviral Drugs. Emerg Infect Dis. 2004;10(4):581–6.

Chen F, Chan KH, Jiang Y, Kao RYT, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31(1):69–75.

Zhao Z, Zhang F, Xu M, Huang K, Zhong W, Cai W, et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. J Med Microbiol. 2003;52(8):715–20.

Morgenstern B, Michaelis M, Baer PC, Doerr HW, Cinatl J. Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun. 2005;326(4):905–8.

Shalhoub S, Farahat F, Al-Jiffri A, Simhairi R, Shamma O, Siddiqi N, et al. IFN-α2a or IFN-β1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: A retrospective study. J Antimicrob Chemother. 2015;70(7):2129–32.

Al Ghamdi M, Alghamdi KM, Ghandoora Y, Alzahrani A, Salah F, Alsulami A, et al. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis [Internet]. 2016;16(1):1–7. Available from: http://dx.doi.org/10.1186/s12879-016-1492-4

Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA. Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) - possible lessons from a systematic review of SARS-CoV therapy. Int J Infect Dis [Internet]. 2013;17(10):e792–8. Available from: http://dx.doi.org/10.1016/j.ijid.2013.07.002

Omrani AS, Memish ZA. Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: How Close Are We? Curr Treat Options Infect Dis. 2015;7(3):202–16.

Lokugamage KG, Hage A, Schindewolf C, Rajsbaum R, Menachery VD, Sprott D. SARS-CoV-2 is sensitive to type I interferon pretreatment. bioRxiv [Internet]. 2020 Jan 1;21(1):2020.03.07.982264. Available from: https://www.golder.com/insights/block-caving-a-viable-alternative/

Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R, et al. Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement. World J Pediatr [Internet]. 2020;(0123456789). Available from: https://doi.org/10.1007/s12519-020-00343-7

Qin X, Qiu S, Yuan Y, Zong Y, Tuo Z, Li J, et al. Clinical Characteristics and Treatment of Patients Infected with COVID-19 in Shishou, China. SSRN Electron J [Internet]. 2020;12. Available from: https://www.ssrn.com/abstract=3541147

U. S. National Institutes of Health. Clinical Trials Database [Internet]. 2020 [cited 2020 Apr 4]. Available from: https://clinicaltrials.gov/

Shiraki K, Daikoku T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol Ther [Internet]. 2020 May;209(January):107512. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0163725820300401

Russian Direct Investment Fund. Russian Ministry of Health approves the first COVID-19 drug Avifavir produced by JV of RDIF and ChemRar [Internet]. 2020 [cited 2020 Jun 1]. Available from: https://rdif.ru/Eng_fullNews/5220/

Vafaei S, Razmi M, Mansoori M, Asadi-Lari M, Madjd Z. Spotlight of Remdesivir in Comparison with Ribavirin, Favipiravir, Oseltamivir and Umifenovir in Coronavirus Disease 2019 (COVID-19) Pandemic. SSRN Electron J [Internet]. 2020;2019. Available from: https://www.ssrn.com/abstract=3569866

Barnard DL, Kumaki Y. Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy. Future Virol [Internet]. 2011 May;6(5):615–31. Available from: https://www.futuremedicine.com/doi/10.2217/fvl.11.33

Alonso H, Bliznyuk AA, Gready JE. Combining docking and molecular dynamic simulations in drug design. Med Res Rev. 2006;26(5):531–68.

Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc. 2016;11(5):905–19.

Lung J, Lin YS, Yang YH, Chou YL, Shu LH, Cheng YC, et al. The potential chemical structure of anti-SARS-CoV-2 RNA-dependent RNA polymerase. J Med Virol. 2020;

Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020;9(1):601–4.

Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020;248:117477.

Rohini S, Vishnupriya P, Rakshagan V, Jain AR. Protective effects of theaflavin. Drug Invent Today. 2018;10(10):2097–101.

Robson B. Computers and viral diseases. Preliminary bioinformatics studies on the design of a synthetic vaccine and a preventative peptidomimetic antagonist against the SARS-CoV-2 (2019-nCoV, COVID-19) coronavirus. Comput Biol Med. 2020;103670.

Choudhary S, Malik YS, Tomar S. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in Silico Structure-Based Virtual Screening Approach. ChemRxiv; 2020.

Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, et al. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015;59(2):1088–99.

Sisk JM, Frieman MB, Machamer CE. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J Gen Virol. 2018;99(5):619–30.

Smith M, Smith JC. Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface. ChemRxiv. 2020;

Ton A-T, Gentile F, Hsing M, Ban F, Cherkasov A. Rapid Identification of Potential Inhibitors of SARS‐CoV‐2 Main Protease by Deep Docking of 1.3 Billion Compounds. Mol Inform. 2020;

Tahir M, Alqahtani SM, Alamri MA, Chen L-L. Structural basis of SARS-CoV-2 3CL pro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal. 2020;(February):1–26.

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B [Internet]. 2020 Feb; Available from: https://doi.org/10.1016/j.apsb.2020.02.008

Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci [Internet]. 2020 Mar;1862(2):117592. Available from: https://doi.org/10.1016/j.bbamem.2019.183135

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 [Internet]. 2020 Mar;(March):2020.01.31.929547. Available from: https://www.biorxiv.org/content/biorxiv/early/2020/02/02/2020.01.31.929547.full.pdf

Received 2020-07-06
Accepted 2020-11-10
Published 2021-01-15