Repositioning drugs for treatment of SARS-CoV-2 / Fármacos reposicionados para tratamento do SARS-CoV-2

Richard de Albuquerque Felizola Romeral, Maria Eduarda Bueno Caldeira, Vanessa Guimarães Alves-Olher, Fabio Vandresen

Abstract


O surgimento de uma nova doença na cidade de Wuhan, centro da China, provocou um estado de calamidade em aspectos globais. As incertezas e escassos estudos até então, levou a Organização Mundial da Saúde declarar estado de pandemia em março de 2020.  Com a elevação exponencial da taxa de novos contágios e o número crescente de óbitos em virtude da SARS-CoV-2, surgiu a necessidade da elaboração de vacinas ou fármacos capazes de contribuir para um tratamento efetivo da doença. Nesse contexto, como o desenvolvimento de novos fármacos específicos é demorado, vários estudos foram iniciados com a utilização de fármacos conhecidos por sua ação terapêutica frente a diferentes doenças e reposicionados como tentativa de tratamento da COVID-19 devido a urgência da atual situação. Mediante o exposto, o presente trabalho trata-se de uma revisão sistemática com base em dados recentes disponibilizados na literatura onde estudos in vivo e in vitro realizados por diferentes autores reportam as possibilidades de fármacos para o tratamento desta doença. 


Keywords


Reposicionamento, SARS-CoV-2, fármacos.

References


Aldini G, Altomare A, Baron G, et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic Res. Vol. 52, p.751-762, 2018.

Antonaccio M J. Angiotensin converting enzyme (ACE) inhibitors. Annual review of pharmacology and toxicology. vol. 22, p.57-87, 1982.

Aquino E M L, Silveira I H, Pescarini J M, et al. Medidas de distanciamento social no controle da pandemia de COVID-19: potenciais impactos e desafios no Brasil. Ciênc. saúde coletiva, Rio de Janeiro. Vol. 25, p. 2423-2446, 2020.

Assimakopoulos S F, Marangos M. N-acetyl-cysteine may prevent COVID-19-associated cytokine storm and acute respiratory distress syndrome. Med Hypotheses. Vol. 140, p. 109778, 2020.

Azevedo T C P, Azevedo P C P, Filho R N S, et al. Use of remdesivir for patients with Covid-19: a review article. Rev. Assoc. Med. Bras. Vol. 66, P. 838-841, 2020.

Backer J A , Klinkenberg D , Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China. Euro Surveill. Vol.25, p.2000062, 2020.

Bai C Q, Mu J S, Kargbo D, et al. Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)-Sierra Leone. Clin Infect Dis. Vol.63, p.1288-1294, 2016.

Bai Y, Yao L, Wei T, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. Vol. 323, p.1406-1407, 2020.

Barrowcliffe T W. Annotation: low molecular weight heparin(s). Br J Haematol. Vol 90, p.1-7, 1995.

Bauer S R, Kapoor A, Rath M, et al. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19?.Cleveland Clin. J.of Medicine. Vol. 87, 2020.

Bavaresco L, Bernardi A, Battastini A M O. Glicocorticoides: Usos clássicos e emprego no tratamento do câncer. Infarma. Vol.17, p.58-60, 2005.

Beigel J H, Tomashek K M, Dodd L E, et al. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020.

Bianchini P, Osima B, Parma B, et al. Structural studies and “in vivo” and “in vitro” pharmacological activities of heparin fractions and fragments prepared by chemical and enzymatic depolimerization. Thromb. Vol. 40, P. 49-58, 1985.

Blaising J, Polyak S J, Pécheur E I. Arbidol as a broad-spectrum antiviral: an update. Antiviral Res. Vol.107, p.84-94, 2014.

Boriskin Y S, Pécheur E I, Polyak S J. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection. Virol J. Vol.3, p.56, 2006.

Cai Q, Yang M, Liu D, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering. 2020.

Cain D W, Cidlowski J A. Immune regulation by glucocorticoids, Nat. Rev. Immunol. Vol. 19, P. 233-247, 2017.

Campochiaro C, Della-Torre E, Cavalli G, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. Eur J Intern Med. Vol. 76, p. 43-49, 2020.

Cao B, Wang Y, Wen D, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. Vol. 382, p.1787-1799, 2020.

Cavalcante BBM, Nascimento ALA, et al. Strategic Management in the fight against COVID-19 in a Supplementary Health Operator in Brazil. Braz J Develop., Vol. 6, p. 28985-28990, 2020.

Chen G, Shi J, Hu Z,et al. Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. Mediators Inflamm. 2008:716458, 2008.

Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. Vol 395, p.507-513, 2020.

Chopra K K, Arora V K. Covid-19 and social stigma: Role of scientific community. Indian J Tuberc.Vol.67, p.284-285, 2020.

Chouchani E T, Kazak L, Jedrychowski M P, et al. Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature. Vol.532, p.112-116, 2016.

Chu C M, Cheng V C, Hung I F, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. Vol.59, p. 252-256, 2004.

Colson P, Raoult D. Fighting viruses with antibiotics: an overlooked path. Int J Antimicrob Agents. Vol. 48, p. 349–352, 2016.

Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19? .J Antimicrob Chemother. Vol.75, p.2013-2014, 2020.

Cvetkovic, R.S., Goa, K.L. Lopinavir/Ritonavir: A Review of its Use in the Management of HIV Infection. Drogas. Vol. 63, p. 769-802, 2003.

Darley E S R, MacGowan A P. Antibiotic treatment of Gram-positive bone and joint infections. J Antimicrob Chemother. Vol. 53, 928– 935, 2004.

Delucia R, Oliveira R M F, Planeta C S, et al. Farmacologia Integrada. 3 Ed. Rio de Janeiro: Livraria e Editora Revinter, 2007. p. 396-492.

Deng L, Li C, Zeng Q, et al. Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study. J Infect.Vol. 81, p.e1-e5, 2020.

Dhabhar F S, miller A H, mcewen B S, et al. Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J. Immunol. Vol. 157, p.1638-1644, 1996.

Dorward J, Gbinigie K. Lopinavir/ritonavir: Uma rápida revisão da eficácia no COVID-19. Disponível em: . Acesso em 06 de outubro de 2020.

Eakin K, Baratz-Goldstein R, Pick CG, et al. Efficacy of N-acetyl cysteine in traumatic brain injury. PLoS One. Vol.9, p. 90617, 2014.

Ellis E F, Dodson L Y, Police R J. Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury. J Neurosurg. Vol. 75, p. 774-779, 1991.

Ezeriņa D, Takano Y, et al. N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production. Cell Chem Biol. Vol. 25, p. 447-459, 2018.

Falavigna M, Colpani V, et al. Diretrizes para o tratamento farmacológico da COVID-19. Consenso da Associação de Medicina Intensiva Brasileira, da Sociedade Brasileira de Infectologia e da Sociedade Brasileira de Pneumologia e Tisiologia. Rev. Bras. Ter. Intensiva. p. 31, p.166-196, 2020.

Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. Vol. 8, p. e21, 2020.

Furuta Y, Gowen BB, Takahashi K,et al. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. Vol.100, .446-454, 2013.

Furuta Y, Takahashi K, Fukuda Y, et al. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother. Vol.46, p.977-981, 2002.

Furuta Y, Takahashi K, Kuno-Maekawa M, et al. Mechanism of action of T-705 against influenza virus. Agentes antimicrob Chemother. Vol.49, p. 981-986, 2005.

Gabay C, Emery P, van Vollenhoven R, Det al. ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. Vol. 381, p. 1541-1550, 2020.

Gagarinova V M, Ignat'eva G S, Sinitskaia L V, et al. The new chemical preparation arbidol: its prophylactic efficacy during flu epidemics. Zh Mikrobiol Epidemiol Immunob. Vol.5, p.40-43, 1993.

Garcia Junqueira D R, Viana T G, Peixoto E R M, et al. Farmacovigilância da heparina no Brasil. Revista Da Associação Médica Brasileira. Vol. 57, p. 328-332, 2011.

Goodman L S, Gilman A G. As bases farmacológicas da terapêutica. 10. ed. Rio de Janeiro: McGraw-Hill, p. 422- 424, 2003.

Gosser T, Smyth E, FitzGerald G A. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. New York. 9rd Ed., p. 617-657, 1997.

Grasselli G, Pesenti A, et al. Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response. JAMA. Vol. 323, p.1545-1546, 2020.

Guan W, Ni Z, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. Vol. 382, p. 1708-1720, 2020.

Hasan S S, Radford S, Kow C S, et al. Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis. J Thromb Thrombolysis. Vol. 3 p. 1-8, 2020.

Hicdonmez T, Kanter M, Tiryaki M, et al. Neuroprotective effects of N-acetylcysteine on experimental closed head trauma in rats. Neurochem Res.Vol. 31,p. 473-481, 2006.

Horby P, L W S, Emberson J, Mafham M, et al. Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report. medRxiv. 2020.

Iba T, Arakawa M, Di Nisio M, et al. Newly Proposed Sepsis-Induced Coagulopathy Precedes International Society on Thrombosis and Haemostasis Overt-Disseminated Intravascular Coagulation and Predicts High Mortality. J Intensive Care Med. Vol. 35, p. 643-649, 2020.

John Hopkins. Coronavirus Resource Center. Disponível em: . Acesso em: 22 de outubro de 2020.

Jorge-Aarón R M, Rosa-Ester M P. N-acetylcysteine as a potential treatment for COVID-19. Future Microbiol. Vol. 15, p. 959-962, 2020.

Kalil A C. Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics. JAMA. Vol.323, p.1897-1898, 2020.

Kaly L., Rosner I. Tocilizumab - a novel therapy for non-organ-specific autoimmune diseases. Best Pract. Res. Clin. Rheumatol. Vol 26, p. 157-165, 2012.

Katzung B G, Masters S B, Trevor A J. Farmacologia Básica e Clínica. 12 Ed. Porto Alegre: AMGH, 2014.

Kimiyasu S, Tohru D. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacology & Therapeutics. Vol. 209, p.107512, 2020.

Kimura A, Kishimoto T. IL-6: Regulator of Treg/Th17 balance. Eur J Immunol. Vol. 40, P.1830-1835, 2010.

Korolkovas A, Burckhalter J H. Química Farmacêutica Rio de Janeiro. Guanabara Koogan, P. 181-217, 1982.

Leneva I A, Fediakina I T, Gus'kova T A, et al. Sensitivity of various strains of influenza virus to arbidol. Influence of the combination of arbidol with different antiviral drugs on the reproduction of influenza A virus. Ter. Arkh. Vol.77, p.84-88,2005.

Li Y, Chen M, Cao H, et al. Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response. Micr. Infect. Vol. 15, p.88-95, 2013.

Lillicrap D. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J Thromb Haemost. Vol. 18, p. 786-787, 2020.

Lima C M A O. Informações sobre o novo coronavírus (COVID-19). Radiol Bras, São Paulo. Vol. 53, p. 5-6, 2020.

Liu Q, Xiong H R, Lu L, et al. Antiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A (H1N1) virus infection. Acta Pharmacol Sin. Vol.34, p.1075-1083, 2013.

Lo M K, Jordan R, Arvey A, et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-and Paramyxoviruses. Sci Rep. Vol. 7, P. 43395, 2017.

Lobo Filho J G , Leitão M C, Lobo R A M, et al. Padronização da dose de heparina sódica utilizada na cirurgia de revascularização do miocárdio sem circulação extracorpórea. Brazilian Journal of Cardiovascular Surgery. Vol. 20, p. 279-285, 2005.

Matthay M A, Zemans R L, Zimmerman G A, et al. Acute respiratory distress syndrome. Nature Reviews Disease Primers. Vol. 18, 2019.

Mendenhall M, Russell A, Juelich T, et al. T-705 (favipiravir) inhibition of arenavirus replication in cell culture. Agentes antimicrob Chemother. Vol. 55, p.782-787, 2011.

Mulangu S, Dodd L E, Davey R T Jr, et al. A randomized, controlled trial of ebola virus disease therapeutics. N Engl J Med. Vol. 381, p. 2293-2303, 2019.

Mycroft-West C, Su D, Pagani I, et al. Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparina. BioRxiv. 2020.

Neville L O, Baillod R A, Brumfitt W, et al. Efficacy and safety of teicoplanin in Gram-positive peritonitis in patients on peritoneal dialysis. Journal of Antimicrobial Chemotherapy. Vol. 21, p. 123–131, 1988.

Nieto-Torres J L, Verdiá-Báguena C, Jimenez-Guardeño J M, et al. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology. Edição 485, P. 330-339, 2015.

Nugent M A. Heparin sequencing brings structure to the function of complex oligosaccharides. Proc Natl Acad Sci U S A. Vol. 97, p. 10301-10303, 2000.

Obrosova-Serova N P, Burtseva E I, Nevskiə I M, et al. The protective action of arbidol during the increase in respiratory diseases in 1990. Vopr Virusol. Vol. 36, p.380-381, 1991.

Okada M, Kitahara M, Kishimoto S, et al. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J Immunol. Vol 151, P.1543-1549, 1988.

Osborne V, Davies M, Lane S, et al. Lopinavir-Ritonavir in the Treatment of COVID-19: A Dynamic Systematic Benefit-Risk Assessment. Drug Saf. Vol.43, p. 809-821, 2020.

Pécheur E I, Borisevich V, Halfmann P, et al. The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses. J Virol. Vol.90, p.3086-3092, 2016.

Queiroz, G. Tocilizumabe para o tratamento de Covid19 severa. Disponível em: < https://pebmed.com.br/tocilizumabe-para-o-tratamento-de-covid-19-severa/ >. Acesso em: 06 de setembro de 2020.

Rang H P, Dale, M M, Ritter J M. Farmacologia. 5. ed. Rio de Janeiro: Editora Guanabara Koogan, p.470-478, 2003.

Remmelts H H, Meijvis S C, Biesma D H, et al. Dexamethasone downregulates the systemic cytokine response in patients with community-acquired pneumonia. Clin Vaccine Immunol. Vol.19, p.1532-1538, 2012.

Reynolds P E. Structure, biochemistry and mechanism of action of glycopeptide antibiotics. Eur. J. of Clin. Microbiol.& Infec. Dis. Vol. 8, p. 943-950, 1989.

Shi C, Wang C, Wang H, et al. The potential of low molecular weight heparin to mitigate cytokine storm in severe covid-19 patients: a retrospective clinical study. medRxiv. P. 20046144, 2020.

Sissoko D, Laouenan C, Folkesson E, et al. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea. PLoS Med. Vol.13, p. e1001967, 2016.

Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. Vol. 371, P.987-997, 2008.

Song Y, Zhang M, Yin L, et al. COVID-19 treatment: close to a cure? A rapid review of pharmacotherapies for the novel coronavirus (SARS-CoV-2). Int J Antimicrob Agents. Vol 56, p. 106080, 2020.

Stewart, S., Yang, K C K., Atkins, K, et al. Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials. Arthritis Research & Therapy. Ed. 1, p. 22-28, 2020.

Tchesnokov E P, Feng J Y, Porter D P, et al. Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir. Viruses. Vol. 11, P. 326, 2019.

Terkeltaub R A. Colchicine update: 2008. Semin Arthritis Rheum. Ed. 38, p. 411-419, 2009.

The Lancet. COVID-19 in Brazil: "So what?". Lancet. Vol.395, p.1461, 2020.

Vaccari S F, Brum J L, Masiero S M K, et al. Avaliação comparativa da atividade biológica de heparinas não-fracionadas em produtos farmacêuticos. Rev. Bras. Hematol. Hemoter. Vol. 25, P. 103-110, 100, 2003.

Valentini S R. “Atributos da Validação da Metodologia Analítica do Captopril num Programa de Garantia de Qualidade”. Disponível em: < https://repositorio.ufsc.br/bitstream /handle/123456789/82411/185613.pdf?sequence=1 > Acesso em 10 de agosto de 2020.

Wan Y, Shang J, Graham R, et al. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decadelong structural studies of SARS. J. Virology. Vol. 94, p. e00127, 2020.

Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. Vol. 323, p. 1061-1069, 2020.

Wang M Z, Cai B Q, Li L Y,et al. Efficacy and safety of arbidol in treatment of naturally acquired influenza. Zhongguo Yi Xue Ke Xue Yuan Xue Bao.Vol.26, p.289-293, 2004.

Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. Vol. 395, p. 1569-1578, 2020.

Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. Vol. 531, p.381-385, 2016.

Yamamura, H, Matsuura H, Nakagawa J, et al. Effect of favipiravir and an anti-inflammatory strategy for COVID-19. Crit Care. Vol.24, p. 413, 2020.

Yang C, Ke C, Yue D, et al. Effectiveness of Arbidol for COVID-19 Prevention in Health Professionals. Front Public Health. Vol.8, p.249, 2020.

Yin Y, Wunderink R G. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. Vol.23, p.130-137, 2018.

Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. Vol. 371, p. 998-1006, 2008.

Zhang J, Ma X, Yu F, et al. Teicoplanin potently blocks the cell entry of 2019-nCoV. BioRxiv. 2020:2020.02.05.935387.

Zhou N, Pan T, Zhang J,et al. Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV). J Biol Chem. Vol. 291, p.9218-9232, 2016.

Zhu N, Zhang D, Wang W, et al. China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China. N Engl J Med. Vol.382, p.727-733, 2020.




DOI: https://doi.org/10.34117/bjdv6n11-081

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