Medicamentos e tratamentos para a Covid-19

Authors

DOI:

https://doi.org/10.1590/s0103-4014.2020.34100.002

Keywords:

Covid-19, Clinical studies, Drugs, Medicinal chemistry, Drug repositioning, Molecular target, Sars-CoV-2

Abstract

Approximately 2,000 clinical studies have been conducted in the world to investigate approved drugs and drug candidates for Covid-19, including small molecules and biologicals, not to mention vaccines. The repositioning of drugs, the most explored strategy, has not led to the identification of any new antiviral against Covid-19. Despite its approval for emergency use by the US regulatory agency, remdesivir has shown only modest results in clinical studies. Dexamethasone, which contributed to reduce mortality in critically ill patients receiving mechanical ventilation or oxygen, is a corticosteroid that has anti-inflammatory and immunosuppressive properties. Biological drugs, such as monoclonal antibodies, interferons, specific proteins, and anticoagulants are being evaluated in several clinical studies to assess their role in Covid-19 therapy. The World Health Organization (WHO) has warned that the coronavirus may never disappear even with the advent of an eventual vaccine, highlighting the urgency for the development of innovative drugs. The most realistic scenario involves the development of specific antivirals against Sars-CoV-2 for the safe and effective treatment of the disease.

Downloads

Download data is not yet available.

Author Biographies

  • FERREIRA LEONARDO L. G, Instituto de Física de São Carlos, Universidade de São Paulo

    Leonardo L. G. Ferreira é pesquisador do Instituto de Física de São Carlos (IFSC) da USP e do Centro de Pesquisa e Inovação em Biodiversidade e Fármacos (CIBFar), um dos Centros de Pesquisa, Inovação e Difusão (Cepid) financiados pela Fapesp.

  • Adriano D. Andricopulo, Instituto de Física de São Carlos, Universidade de São Paulo

    Adriano D. Andricopulo é professor titular do Instituto de Física de São Carlos (IFSC) da USP, coordenador de Transferência de Tecnologia do Centro de Pesquisa e Inovação em Biodiversidade e Fármacos (CIBFar), um dos Centros de Pesquisa, Inovação e Difusão (Cepid) financiados pela Fapesp, e diretor executivo da Academia de Ciências do Estado de São Paulo (Aciesp).

References

BAUM, A. et al. Antibody cocktail to Sars-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science, v.369, n.6506, p.1014-18, 2020.

BIRAN, N. et al. Tocilizumab among patients with Covid-19 in the intensive care unit:

a multicentre observational study. Lancet Rheumatol., 2020. No prelo. doi: 10.1016/

S2665-9913(20)30277-0. Disponível em: <https://www.thelancet.com/journals/

lanrhe/article/PIIS2665-9913(20)30277-0/fulltext>. Acesso em: 28 set. 2020.

CAO, B, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19.

N. Engl. J. Med., v.382, n.19, p.1787-99, 2020.

CHEN, L. et al. Convalescent plasma as a potential therapy for Covid-19. Lancet Infect.

Dis., v.20, n.4, p.398-400, 2020.

COHEN, J. Antibodies may curb pandemic before vaccines. Science, v.369, n.6505,

p.752-3, 2020.

CUI, J. et al. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol.,

v.17, n.3, p.181-92, 2019.

DE ROSSI, N. et al. Early use of low dose tocilizumab in patients with Covid-19:

A retrospective cohort study with a complete follow-up. EClinicalMedicine, v.25,

p.100459, 2020.

DiMASI, J. A. Research and development costs of new drugs. JAMA, v.324, n.5, p.517,

DOWDEN, H.; MUNRO J. Trends in clinical success rates and therapeutic focus. Nat.

Rev. Drug Discov., v.18, n.7, p.495-6, 2019.

FERREIRA, L. G.; ANDRICOPULO, A. D. Drug repositioning approaches to parasitic diseases: a medicinal chemistry perspective. Drug Discov. Today, v.21, n.10, p.1699-

, 2016.

FERREIRA, L. G.; ANDRICOPULO, A. D. Covid-19: Small-molecule clinical trials

landscape. Curr. Top. Med. Chem., v.20, n.18, p.1577-80, 2020.

FLEXNER, C. HIV-protease inhibitors. N. Engl. J. Med., v.338, n.18, p.1281-92,

FLORINDO, H. F. et al. Immune-mediated approaches against Covid-19. Nat. Nanotechnol., v.15, n.8, p.630-45, 2020.

FUNNELL, S. G. P. et al. Emerging preclinical evidence does not support broad use

of hydroxychloroquine in Covid-19 patients. Nat. Commun., v.11, n.1, p.4253, 2020.

FURLOW, B. Covacta trial raises questions about tocilizumab’s benefit in Covid-19.

Lancet Rheumatol., v.2, n.10, p.e592, 2020.

GHAHREMANPOUR, M. M. et al. Identification of 14 known drugs as inhibitors of the main protease of Sars-CoV-2. bioRxiv, 2020. Pré-print. doi:

1101/2020.08.28.271957. Disponível em: <https://www.biorxiv.org/content/1

1101/2020.08.28.271957v1>. Acesso em: 28 set. 2020.

GHOFRANI, H. A.; OSTERLOH, I. H.; GRIMMINGER F. Sildenafil: from angina

to erectile dysfunction to pulmonary hypertension and beyond. Nat. Rev. Drug Discov.,

v.5, n.8, p.689-702, 2006.

GORDON, et al. A Sars-CoV-2 protein interaction map reveals targets for drug repurposing. Nature, v.583, n.7816, p.459-68, 2020.

HANSEN, J. et al. Studies in humanized mice and convalescent humans yield a Sars-

-CoV-2 antibody cocktail. Science, v.369, n.6506, p.1010-14, 2020.

HARRISON, C. Coronavirus puts drug repurposing on the fast track. Nat. Biotechnol.,

v.38, n.4, p.379-81, 2020.

HILLEN, H. S. et al. Structure of replicating Sars-CoV-2 polymerase. Nature, v.584,

n.7819, p.154-6, 2020.

HUANG, Y. et al. Structural and functional properties of Sars-CoV-2 spike protein:

potential antivirus drug development for Covid-19. Acta Pharmacol. Sin., v.41, n.9,

p.1141-9, 2020.

HUNG, I. F. 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, v.395, n.10238, p.1695-1704, 2020.

JIN, Z. et al. Structure of Mpro from Sars-CoV-2 and discovery of its inhibitors. Nature, v.582, n.7811, p.289-93, 2020.

JOMAH, S.; ASDAQ, S. M. B.; AL-YAMANI, M. J. Clinical efficacy of antivirals against

novel coronavirus (Covid-19): A review. J. Infect. Public Health., v.13, n.9, p.1187-95,

KEWAN, T. et al. Tocilizumab for treatment of patients with severe Covid-19: A retrospective cohort study. EClinicalMedicine, v.24, p.100418, 2020.

KISHIMOTO, T. K. et al. Improving the efficacy and safety of biologic drugs with

tolerogenic nanoparticles. Nat. Nanotechnol., v.11, n.10, p.890-9, 2016.

KUPFERSCHMIDT, K.; COHEN, J. Race to find Covid-19 treatments accelerates.

Science, v.367, n.6485, p.1412-1413, 2020.

LEDFORD, H. Evidence lags behind excitement over blood plasma as a coronavirus

treatment. Nature, v.584, n.7822, p.505, 2020.

LIU, J. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in

inhibiting Sars-CoV-2 infection in vitro. Cell Discov., v.6, n.16, 2020.

MAISONNASSE, P. et al. Hydroxychloroquine use against Sars-CoV-2 infection in

non-human primates. Nature, v.585, n.7826, p.584-587, 2020.

MONTEIL, V. et al. Inhibition of Sars-CoV-2 infections in engineered human tissues

using clinical-grade soluble human ACE2. Cell, v.181, n.4, p.905-13.e7, 2020.

MURRAY, C. W. et al. A successful collaboration between academia, biotech and pharma led to discovery of erdafitinib, a selective FGFR inhibitor recently approved by the

FDA. MedChemComm, v.10, n.9, p.1509-11, 2019.

NATIONAL INSTITUTES OF HEATH (NIH). Disponível em: .

Acesso em: 28 set. 2020.

NOMURA, S. et al. Discovery of canagliflozin, a novel C-glucoside with thiophene

ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type

diabetes mellitus. J. Med. Chem., v.53, n.17, p.6355-60, 2010.

NORMAND, S. T. The RECOVERY platform. N. Engl. J. Med., 2020. doi:10.1056/

NEJMe2025674. Disponível em: <https://www.nejm.org/doi/full/10.1056/NEJMe2025674>. Acesso em: 28 set. 2020.

PACKARD, R. M. The origins of antimalarial-drug resistance. N. Engl. J. Med., v.371

n.5, p.397-9, 2014.

PUSHPAKOM, S. et al. Drug repurposing: progress, challenges and recommendations.

Nat. Rev. Drug Discov., v.18, n.1, p.41-58, 2019.

RECOVERY Collaborative Group et al. Dexamethasone in hospitalized patients with

Covid-19 - preliminary report. N. Engl. J. Med., 2020. doi: 10.1056/NEJMoa2021436.

Disponível em: <https://www.nejm.org/doi/10.1056/NEJMoa2021436>. Acesso

em: 28 set. 2020).

ROSENBERG, E. S. et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with Covid-19 in New York State.

JAMA, v.323, n.24, p.2493-502, 2020.

SCHERMULY, R.T. et al. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur. Respir. J., v.32, n.4, p.881-91, 2008.

SHEAHAN, T. P. et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and

zoonotic coronaviruses. Sci. Transl. Med., v.9, n.396, p.eaal3653, 2017.

SHIN, D. et al. Papain-like protease regulates Sars-CoV-2 viral spread and innate immunity. Nature, 2020. doi: 10.1038/s41586-020-2601-5. Disponível em:

www.nature.com/articles/s41586-020-2601-5>. Acesso em: 28 set. 2020.

SMITH, B. D. et al. Ripretinib (DCC-2618) is a switch control kinase inhibitor of a

broad spectrum of oncogenic and drug-resistant KIT and PDGFRA variants. Cancer

Cell, v.35, n.5, p.738-51.e9, 2019.

SOFIA, M. J. et al. Discovery of a -d-2’-deoxy-2’- -fluoro-2’- -C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. J. Med. Chem., v.53,

n.19, p.7202-18, 2010.

TANDON, R. et al. Effective Inhibition of Sars-CoV-2 entry by heparin and enoxaparin derivatives. bioRxiv, 2020. Pré-print. doi: 10.1101/2020.06.08.140236. Disponível em: <https://www.biorxiv.org/content/10.1101/2020.06.08.140236v1>.

Acesso em: 28 set. 2020.

THE LANCET INFECTIOUS DISEASES. Curing Covid-19. Lancet Infect. Dis.,

doi: 10.1016/S1473-3099(20)30706-4. Disponível em: <https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30706-4/fulltext>. Acesso em:

set. 2020.

TU, X. et al. Structural basis of HIV-1 resistance to AZT by excision. Nat. Struct. Mol.

Biol., v.17, n.10, p.1202-1209, 2010.

VAN GOOR, F. et al. Rescue of CF airway epithelial cell function in vitro by a CFTR

potentiator, VX-770. Proc. Natl. Acad .Sci. U. S. A., v.106, n.44, p.18825-30, 2009.

WARREN, T. K. et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature, v.531, n.7594, 381-385, 2016.

WELKER, A. et al. SAR of novel benzamides and isoindolines, designed as SARS-CoV

protease inhibitors - effective against Sars-CoV-2. ChemMedChem, 2020. doi:10.1002/

cmdc.202000548. Disponível em: <https://chemistry-europe.onlinelibrary.wiley.

com/doi/10.1002/cmdc.202000548>. Acesso em: 28 set. 2020.

WERMUTH, C. G. et al. Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., v.70, n.5, p.1129-1143, 1998.

WORLD HEALTH ORGANIZATION (WHO). Coronavirus disease (Covid-19) pandemic. Disponível em: <https://www.who.int/emergencies/diseases/novel-coronavirus-2019>. Acesso em: 27 set. 2020.

WORLD HEALTH ORGANIZATION (WHO). WHO Coronavirus Disease (Covid-19) Dashboard. Disponível em: <https://covid19.who.int/>. Acesso em: 27 set.

ZAKI, A. M. et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi

Arabia. N. Engl. J. Med., v.367, n.19, p.1814-20, 2012.

ZELIKIN, A. N.; EHRHARDT, C.; HEALY, A. M. Materials and methods for delivery

of biological drugs. Nat. Chem., v.8, n.11, p.997-1007, 2016.

ZHONG, N. S. et al. Epidemiology and cause of severe acute respiratory syndrome

(SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet, v.362,

n.9393, p.1353-1358, 2003.

ZHOU, Y. et al. Network-based drug repurposing for novel coronavirus 2019-nCoV/

Sars-CoV-2. Cell Discov., v.6, n.1, p.1-18, 2020.

ZHU, N. et al. A Novel Coronavirus from patients with pneumonia in China, 2019. N.

Engl. J. Med., v.382, n.8, p.727-33, 2020.

ZOST, S. J. et al. Potently neutralizing and protective human antibodies against Sars-

-CoV-2. Nature, v.584, n.7821, p.443-9, 2020.

Published

2020-12-01

Issue

Section

Impacts of the pandemic

How to Cite

LEONARDO L. G, F., & Andricopulo, A. D. (2020). Medicamentos e tratamentos para a Covid-19. Estudos Avançados, 34(100), 7-27. https://doi.org/10.1590/s0103-4014.2020.34100.002