TARGET KERJA OBAT COVID-19: REVIEW

Purwaniati Purwaniati, Aiyi Asnawi

Sari


Corona virus desease 2019 (COVID-19) yang disebabkan Severe acute respiratory syndrome Corona Virus 2 (SARS-CoV-2) telah menjadi wabah global. Hingga saat belum ada obat atau vaksin untuk terapi COVID-19 ini. Upaya penemuan obat baru atau pengujian terhadap obat yang telah ada mendesak untuk dilakukan. Penentuan target kerja obat COVID-19 yang tepat menjadi tantangan tersendiri, karena sebagai virus baru strukturnya belum diketahui secara jelas. Dalam kesempatan ini, kami melakukan sistematik review untuk dapat mengidentifikasi molekul-molekul yang dapat menjadi target kerja obat anti COVID-19. Review ini diawali dengan penelusuran pustaka pada database Pubmed dengan menggunakan kata kunci “SARS-CoV-2 drug targetâ€. Main protease (Mpro), angiotensin converting enzyme 2 (ACE2), protein spike dan RNA-dependent RNA polymerase (RdRp) merupakan protein target yang paling banyak digunakan dalam penelitian.

Kata Kunci


Target Kerja SARS-CoV-2, COVID-19, Virus Corona

Teks Lengkap:

PDF (English)

Referensi


Antoniak, S. et al. 2017. Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced Cardiovascular Remodeling and Inflammation. Cardiology (Switzerland). doi: 10.1159/000452269.

Basit, A., Ali, T. and Rehman, S. U. 2020. Truncated human Angiotensin Converting Enzyme 2; a potential inhibitor of SARS-CoV-2 spike glycoprotein and potent COVID-19 therapeutic agent. Journal of Biomolecular Structure and Dynamics. doi: 10.1080/07391102.2020.1768150.

Belouzard, S. et al. 2012. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. doi: 10.3390/v4061011.

Cao, Y. et al. 2020. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients B cells. Cell. doi: 10.1016/j.cell.2020.05.025.

Channappanavar, R. and Perlman, S. 2017. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars in Immunopathology. doi: 10.1007/s00281-017-0629-x.

Chen, X. et al. 2014. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein and Cell. doi: 10.1007/s13238-014-0026-3.

Chen, Y. et al. 2011. ‘Biochemical and structural insights into the mechanisms of sars coronavirus RNA ribose 2′-O-methylation by nsp16/nsp10 protein complex. PLoS Pathogens. doi: 10.1371/journal.ppat.1002294.

Cicerale, S. et al. 2009. Chemistry and health of olive oil phenolics. Critical Reviews in Food Science and Nutrition. doi: 10.1080/10408390701856223.

Davies, J. et al. 2004. Quantitative structure-activity relationship modeling of acute toxicity of quaternary alkylammonium sulfobetaines to Daphnia magna. Environmental Toxicology and Chemistry, 23(9), pp. 2111–2115. doi: 10.1897/03-312.

Elmezayen, A. D. et al. 2020. Drug repurposing for coronavirus (COVID-19): in silico screening of known drugs against coronavirus 3CL hydrolase and protease enzymes. Journal of biomolecular structure & dynamics. doi: 10.1080/07391102.2020.1758791.

Emameh, R. Z., Nosrati, H. and Taheri, R. A. 2020. Combination of biodata mining and computational modelling in identification and characterization of ORF1ab polyprotein of SARS-CoV-2 isolated from oronasopharynx of an Iranian patient. Biological Procedures Online. doi: 10.1186/s12575-020-00121-9.

Enmozhi, S. K. et al. 2020. Andrographolide As a Potential Inhibitor of SARS-CoV-2 Main Protease: An In Silico Approach. Journal of biomolecular structure & dynamics. doi: 10.1080/07391102.2020.1760136.

Ferrario, C. M. and Mullick, A. E. 2017. Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease. Pharmacological Research. doi: 10.1016/j.phrs.2017.05.020.

Fujii, S. and Hitomi, Y. 1981. New synthetic inhibitors of C1r̄, C1 esterase, thrombin, plasmin, kallikrein and trypsin. BBA - Enzymology. doi: 10.1016/0005-2744(81)90023-1.

Gao, Y. et al. 2020. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. doi: 10.1126/science.abb7498.

Gheblawi, M. et al. 2020. Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circulation research. doi: 10.1161/CIRCRESAHA.120.317015.

Gimeno, A. et al. (2020) ‘Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition.’, International journal of molecular sciences, 21(11). doi: 10.3390/ijms21113793.

Gordon, C. J. et al. 2020. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Journal of Biological Chemistry. doi: 10.1074/jbc.ra120.013679.

Gurung, A. B. et al. 2020. Unravelling lead antiviral phytochemicals for the inhibition of SARS-CoV-2 Mpro enzyme through in silico approach. Life Sciences. Elsevier, 255(May), p. 117831. doi: 10.1016/j.lfs.2020.117831.

Harcourt, B. H. et al. 2004. Identification of Severe Acute Respiratory Syndrome Coronavirus Replicase Products and Characterization of Papain-Like Protease Activity. Journal of Virology. doi: 10.1128/jvi.78.24.13600-13612.2004.

Haschke, M. et al. 2013. Pharmacokinetics and pharmacodynamics of recombinant human angiotensin-converting enzyme 2 in healthy human subjects. Clinical Pharmacokinetics. doi: 10.1007/s40262-013-0072-7.

Hilgenfeld, R. 2014. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS journal. doi: 10.1111/febs.12936.

Hoffmann, M., Schroeder, S., et al. 2020. Nafamostat mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrobial agents and chemotherapy. doi: 10.1128/AAC.00754-20.

Hoffmann, M., Kleine-Weber, H., et al. 2020. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. doi: 10.1016/j.cell.2020.02.052.

Holshue, M. L. et al. 2020. First case of 2019 novel coronavirus in the United States. New England Journal of Medicine. doi: 10.1056/NEJMoa2001191.

Huang, C. et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. doi: 10.1016/S0140-6736(20)30183-5.

Hudson, C. B. and Beaudette, F. R. 1932. Infection of the cloaca with the virus of infectious bronchitis. Science. doi: 10.1126/science.76.1958.34-a.

Imai, Y. et al. 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. doi: 10.1038/nature03712.

Ivanov, K. A. and Ziebuhr, J. 2004. Human Coronavirus 229E Nonstructural Protein 13: Characterization of Duplex-Unwinding, Nucleoside Triphosphatase, and RNA 5′-Triphosphatase Activities. Journal of Virology. doi: 10.1128/jvi.78.14.7833-7838.2004.

Iwata-Yoshikawa, N. et al. 2019. TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. Journal of Virology. doi: 10.1128/jvi.01815-18.

Jin, Z., Zhao, Y., et al. 2020. Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur. Nature structural & molecular biology. doi: 10.1038/s41594-020-0440-6.

Jin, Z., Du, X., et al. 2020. Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. Springer US. doi: 10.1038/s41586-020-2223-y.

Joshi, R. S. et al. 2020. Discovery of Potential Multi-Target-Directed Ligands by Targeting Host-specific SARS-CoV-2 Structurally Conserved Main Protease$. Journal of biomolecular structure & dynamics. doi: 10.1080/07391102.2020.1760137.

Khan, A. et al. 2017. A pilot clinical trial of recombinant human angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Critical Care. doi: 10.1186/s13054-017-1823-x.

Kuo, L., Hurst, K. R. and Masters, P. S. 2007. Exceptional Flexibility in the Sequence Requirements for Coronavirus Small Envelope Protein Function. Journal of Virology. doi: 10.1128/jvi.01577-06.

Kupferschmidt, K. 2020. These drugs don’t target the coronavirus—they target us. Science. doi: 10.1126/science.abc0405.

Li, S. W. et al. 2016. SARS coronavirus papain-like protease inhibits the TLR7 signaling pathway through removing Lys63-linked polyubiquitination of TRAF3 and TRAF6. International Journal of Molecular Sciences. doi: 10.3390/ijms17050678.

Li, X. et al. 2020. Molecular immune pathogenesis and diagnosis of COVID-19. Journal of Pharmaceutical Analysis. Elsevier Ltd, 10(2), pp. 102–108. doi: 10.1016/j.jpha.2020.03.001.

Lu, R. et al. 2020. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. doi: 10.1016/S0140-6736(20)30251-8.

Luk, H. K. H. et al. 2019. Molecular epidemiology, evolution and phylogeny of SARS coronavirus. Infection, Genetics and Evolution. doi: 10.1016/j.meegid.2019.03.001.

McBride, R., van Zyl, M. and Fielding, B. C. 2014. The coronavirus nucleocapsid is a multifunctional protein. Viruses. doi: 10.3390/v6082991.

Meenakshisundaram, B. and Robert, S. R. 2020. Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins. chemRxiv. doi: 10.26434/chemrxiv.12084822.v1.

Mirza, M. U. and Froeyen, M. 2020. Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2020.04.008.

Morse, J. S. et al. 2020. Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV. ChemBioChem. doi: 10.1002/cbic.202000047.

Nutho, B. et al. 2020. Why are lopinavir and ritonavir effective against the newly emerged coronavirus 2019? Atomistic insights into the inhibitory mechanisms. Biochemistry. doi: 10.1021/acs.biochem.0c00160.

Okada, M. et al. 2005. The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice. Vaccine, 23(17–18), pp. 2269–2272. doi: 10.1016/j.vaccine.2005.01.036.

Oudit, G. Y. et al. 2009. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. European Journal of Clinical Investigation. doi: 10.1111/j.1365-2362.2009.02153.x.

Pinto, D. et al. 2020. Structural and functional analysis of a potent sarbecovirus neutralizing antibody. bioRxiv. doi: 10.1101/2020.04.07.023903.

Plewczynski, D. et al. 2007. In silico prediction of SARS protease inhibitors by virtual high throughput screening. Chemical Biology and Drug Design. doi: 10.1111/j.1747-0285.2007.00475.x.

Prajapat, M. et al. 2020. Drug targets for corona virus: A systematic review. Indian Journal of Pharmacology. doi: 10.4103/ijp.IJP_115_20.

Quimque, M. T. J. et al. 2020. Not One, But Five: Virtual Screening-Driven Drug Discovery of SARS-CoV2 Enzyme Inhibitors Targeting Viral Attachment, Replication and Post-Translational Infection Mechanisms. ChemRxiv. doi: 10.26434/chemrxiv.12170424.v1.

Reiner, Ž. et al. 2020. Statins and the COVID-19 main protease: in silico evidence on direct interaction. Archives of Medical Science. doi: 10.5114/aoms.2020.94655.

Rut, W. et al. 2020. Activity profiling of SARS-CoV-2-PLpro protease provides structural framework for anti-COVID-19 drug design. bioRxiv. doi: 10.1101/2020.04.29.068890.

Schoeman, D. and Fielding, B. C. 2019. Coronavirus envelope protein: Current knowledge. Virology Journal. doi: 10.1186/s12985-019-1182-0.

Shamsi, A. et al. 2020. Glecaprevir and Maraviroc are high-affinity inhibitors of SARS-CoV-2 main protease: Possible therapeutic implication in COVID-19. Bioscience reports, 0(June), pp. 1–8. doi: 10.1042/BSR20201256.

Shum, K. T. and Tanner, J. A. 2008 Differential inhibitory activities and stabilisation of DNA aptamers against the SARS coronavirus helicase. Chembiochem : a European journal of chemical biology. doi: 10.1002/cbic.200800491.

Simmons, G. et al. 2004. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proceedings of the National Academy of Sciences of the United States of America. doi: 10.1073/pnas.0306446101.

Subissi, L. et al. 2014. One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities. Proceedings of the National Academy of Sciences of the United States of America. doi: 10.1073/pnas.1323705111.

Tsuji, M. 2020. Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease. FEBS open bio. doi: 10.1002/2211-5463.12875.

Umesh et al. 2020. Identification of new anti-nCoV drug chemical compounds from Indian spices exploiting SARS-CoV-2 main protease as target. Journal of Biomolecular Structure and Dynamics. Taylor & Francis, 0(0), pp. 1–9. doi: 10.1080/07391102.2020.1763202.

Venkatagopalan, P. et al. 2015. Coronavirus envelope (E) protein remains at the site of assembly. Virology. doi: 10.1016/j.virol.2015.02.005.

Walls, A. C. et al. 2020. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. doi: 10.1016/j.cell.2020.02.058.

Wan, Y. et al. 2020 Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Journal of Virology. doi: 10.1128/jvi.00127-20.

Wang, M. et al. 2020. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research. doi: 10.1038/s41422-020-0282-0.

Wang, M. Y. et al. 2018. A comprehensive in silico method to study the QSTR of the aconitine alkaloids for designing novel drugs. Molecules. doi: 10.3390/molecules23092385.

Wang, Q. M. et al. 1997 A continuous colorimetric assay for rhinovirus-14 3C protease using peptide p-nitroanilides as substrates. Analytical Biochemistry. doi: 10.1006/abio.1997.2315.

Wang, Y. and Liu, L. 2016. The membrane protein of severe acute respiratory syndrome coronavirus functions as a novel cytosolic pathogen-associated molecular pattern to promote beta interferon induction via a toll-like-receptor-related TRAF3-independent mechanism. mBio. doi: 10.1128/mBio.01872-15.

Weiss, S. R. and Leibowitz, J. L. 2011. Coronavirus pathogenesis. 1st edn, Advances in Virus Research. 1st edn. Elsevier Inc. doi: 10.1016/B978-0-12-385885-6.00009-2.

Williams, A. E. and Chambers, R. C. 2014. The mercurial nature of neutrophils: Still an enigma in ARDS?. American Journal of Physiology - Lung Cellular and Molecular Physiology. doi: 10.1152/ajplung.00311.2013.

De Wit, E. et al. 2016. SARS and MERS: Recent insights into emerging coronaviruses. Nature Reviews Microbiology. doi: 10.1038/nrmicro.2016.81.

Wrapp, D. et al. 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. doi: 10.1126/science.aax0902.

Wu, C. et al. .2020. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. doi: 10.1016/j.apsb.2020.02.008.

Wu, K. et al. 2012. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. Journal of Biological Chemistry. doi: 10.1074/jbc.M111.325803.

Xu, Z. et al. 2020. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. doi: 10.1016/S2213-2600(20)30076-X.

Xue, X. et al. 2007. Production of Authentic SARS-CoV Mpro with Enhanced Activity: Application as a Novel Tag-cleavage Endopeptidase for Protein Overproduction. Journal of Molecular Biology. doi: 10.1016/j.jmb.2006.11.073.

Yamamoto, M. et al. 2016. Identification of nafamostat as a potent inhibitor of middle east respiratory syndrome Coronavirus s protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrobial Agents and Chemotherapy. doi: 10.1128/AAC.01043-16.

Yang, H., Bartlam, M. and Rao, Z. 2006. Drug Design Targeting the Main Protease, the Achilles Heel of Coronaviruses’, Current Pharmaceutical Design. doi: 10.2174/138161206779010369.

Yu, L. et al. 2016. Angiotensin-(1-5), an active mediator of renin-angiotensin system, stimulates ANP secretion via Mas receptor. Peptides. doi: 10.1016/j.peptides.2016.09.009.

Yuan, L. et al. 2015. P53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling. Journal of Biological Chemistry. doi: 10.1074/jbc.M114.619890.

Zhang, H. and Baker, A. 2017. Recombinant human ACE2: Acing out angiotensin II in ARDS therapy. Critical Care. doi: 10.1186/s13054-017-1882-z.

Zhang, L., Lin, D., Sun, X., Curth, U., et al. 2020. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved a-ketoamide inhibitors. Science. doi: 10.1126/science.abb3405.

Zhang, L., Lin, D., Sun, X., Rox, K., et al. 2020. X-ray Structure of Main Protease of the Novel Coronavirus SARS-CoV-2 Enables Design of α-Ketoamide Inhibitors. bioRxiv. doi: 10.1101/2020.02.17.952879.

Zhou, P. et al. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. Springer US, 579(7798), pp. 270–273. doi: 10.1038/s41586-020-2012-7.

Zhou, Y. et al. 2010. A Single Asparagine-Linked Glycosylation Site of the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Facilitates Inhibition by Mannose-Binding Lectin through Multiple Mechanisms. Journal of Virology. doi: 10.1128/jvi.00554-10.




DOI: http://dx.doi.org/10.47653/farm.v7i2.172

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