Prediction of SARS-CoV-2 3C-like protease (3CLpro) crystal structure to provide COVID-19 inhibitor design through computational studies
AbstractInfectious diseases have lately become pandemic, posing a threat to global public health with the introduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously provisionally named 2019 novel coronavirus or 2019-nCoV). Technological advancements have increased the possibility of discovering natural inhibitor candidates capable of preventing and controlling COVID-19 infections. The SARS-CoV-2 3C-like protease (3CLpro) is critical for SARS-CoV-2 replication and is a prospective therapeutic target. This study aims to identify, evaluate, and explore the 3CLpro macromolecular structures from SARS-CoV and SARS-CoV-2, as well as their impact on angiotensin-converting enzyme 2 (ACE-2). The discovery of the two 3CLpro macromolecules revealed structural similarities in several regions. These findings were subsequently confirmed by performing protein-protein docking simulations to observe the interaction of 3CLpro with the active site ACE-2. With an ACE score of 701.41 kJ/mol, SARS-COV-2 3CLpro forms the strongest binding with ACE-2. As a result, the findings of this research can be used to guide the development of potential SARS-CoV-2 3CLpro inhibitors for the treatment of COVID-19 infectious diseases.
Alamri MA, Ul Qamar MT, Mirza MU, Bhadane R, Alqahtani SM, Muneer I, Froeyen M, Salo-Ahen OMH. 2021. Pharmacoinformatics and molecular dynamics simulation studies reveal potential covalent and FDA-approved inhibitors of SARS-CoV-2 main protease 3CLpro. Journal of Biomolecular Structure and Dynamics. vol 39(13): 4936–4948. doi: https://doi.org/10.1080/07391102.2020.1782768.
Alipoor SD, Mortaz E, Jamaati H, Tabarsi P, Bayram H, Varahram M, Adcock IM. 2021. COVID-19: Molecular and Cellular Response. Frontiers in Cellular and Infection Microbiology. vol 11: 1–16. doi: https://dx.doi.org/10.3389%2Ffcimb.2021.563085.
Ansari MA, Jamal QMS, Rehman S, Almatroudi A, Alzohairy MA, Alomary MN, Tripathi T, Alharbi AH, Adil SF, Khan M, Malik MS. 2020. TAT-peptide conjugated repurposing drug against SARS-CoV-2 main protease (3CLpro): Potential therapeutic intervention to combat COVID-19. Arabian Journal of Chemistry. vol 13(11): 8069–8079. doi: https://doi.org/10.1016/j.arabjc.2020.09.037.
Banerjee A, Kanwar M, Maiti S. 2021. Theaflavin-3’-O-gallate a black-tea constituent blocked SARS CoV-2 RNA dependant RNA polymerase active-site with better docking results than remdesivir. Drug Research. vol 71(8): 462–472. doi: https://doi.org/10.1055/a-1467-5828.
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. 2000. The protein data bank. Nucleic Acids Research. vol 28(1): 235–242. doi: https://doi.org/10.1093/nar/28.1.235.
BIOVA DS. 2020. Discovery studio modeling environment, release 2020. San Diego: Dassault Systemes. https://www.3ds.com.
Camacho CJ, Gatchell DW, Kimura SR, Vajda S. 2000. Scoring docked conformations generated by rigid‐body protein‐protein docking. Proteins: Structure, Function, and Bioinformatics. vol 40(3): 525–537. doi: https://doi.org/10.1002/1097-0134(20000815)40:3%3C525::AID-PROT190%3E3.0.CO;2-F.
Chan JFW, Yuan S, Kok KH, To KKW, Chu H, Yang J, Xing F, Liu J, Yip CCY, Poon RWS, Tsoi HW, Lo SKF, Chan KH, Poon VKM,
Chan WM, Daniel J, Cai JP, Cheng VCC, Yuen KY. 2020. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. vol 395(10223): 514–523. doi: https://doi.org/10.1016/S0140-6736(20)30154-9.
Chen YW, Yiu CPB, Wong KY. 2020. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000Research. vol 9: 1–17. doi: https://doi.org/10.12688/f1000research.22457.2.
Fakih TM. 2020a. Dermaseptin-based antiviral peptides to prevent COVID-19 through in silico molecular docking studies against SARS-Cov-2 spike protein. Pharmaceutical Sciences & Research. vol 7(4): 65–70. doi: https://doi.org/10.7454/psr.v7i4.1079.
Fakih TM, Dewi ML, Syahroni E. 2020b. Magainin as an antiviral peptide of SARS-CoV-2 main protease for potential inhibitor: an in silico approach. Biogenesis: Jurnal Ilmiah Biologi. vol 8(1): 104–110. doi: https://doi.org/10.24252/bio.v8i1.13871.
Graham RL, Becker MM, Eckerle LD, Bolles M, Denison MR, Baric RS. 2012. A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease. Nature Medicine. vol 18(12): 1820–1926. doi: https://doi.org/10.1038/nm.2972.
Guzzi PH, Mercatelli D, Ceraolo C, Giorgi FM. 2020. Master regulator analysis of the SARS-CoV-2/human interactome. Journal of Clinical Medicine. vol 9(4): 1–15. doi: https://doi.org/10.3390/jcm9040982.
ICTV. 2020. Naming the 2019 Coronavirus. London: International Committee on Taxonomy of Viruses. https://talk.ictvonline.org/.
Mohammad S, Bouchama A, Alharbi BM, Rashid M, Khatlani TS, Gaber NS, Malik SS. 2020. SARS-CoV-2 ORF8 and SARS-CoV ORF8ab: genomic divergence and functional convergence. Pathogens. vol 9(9): 1–25. doi: https://doi.org/10.3390/pathogens9090677.
Kumar S, Maurya VK, Prasad AK, Bhatt MLB, Saxena SK. 2020. Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV). Virusdisease. vol 31(1): 13–21. doi: https://doi.org/10.1007/s13337-020-00571-5.
Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, Gao GF. 2017. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV. Antiviral Research. vol 137: 82–92. doi: https://doi.org/10.1016/j.antiviral.2016.11.006.
Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC, Daniels AD, Jervey S, Albaiu D. 2020. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Central Science. vol 6(3): 315–331. doi: https://doi.org/10.1021/acscentsci.0c00272.
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Tan W. 2020. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. vol 395(10224): 565–574. doi: https://doi.org/10.1016/S0140-6736(20)30251-8.
Ng OW, Chia A, Tan AT, Jadi RS, Leong HN, Bertoletti A, Tan YJ. 2016. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection. Vaccine. vol 34(17): 2008–2014. doi: https://doi.org/10.1016/j.vaccine.2016.02.063.
Pachetti M, Marini B, Benedetti F, Giudici F, Mauro E, Storici P, Masciovecchio C, Angeletti S, Ciccozzi M, Gallo RC, Zella D. 2020. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. Journal of Translational Medicine. vol 18(1): 1–9. doi: https://doi.org/10.1186/s12967-020-02344-6.
Prajapat M, Sarma P, Shekhar N, Avti P, Sinha S, Kaur H, Kumar S, Bhattacharyya A, Kumar H, Bansal S, Medhi B. 2020. Drug targets for corona virus: A systematic review. Indian Journal of Pharmacology. vol 52(1): 56–65. doi: https://dx.doi.org/10.4103%2Fijp.IJP_115_20.
Rajpoot S, Alagumuthu M, Baig MS. 2021. Dual targeting of 3CLpro and PLpro of SARS-COV-2: a novel structure-based design approach to treat Covid-19. Current Research in Structural Biology. vol 3: 9–18. doi: https://doi.org/10.1016/j.crstbi.2020.12.001.
Ramadhan DS, Fakih TM, Arfan A. 2020. Activity prediction of bioactive compounds contained in Etlingera elatior against the SARS-CoV-2 main protease: An in silico approach. Borneo Journal of Pharmacy. vol 3(4): 235–242. doi: https://doi.org/10.33084/bjop.v3i4.1634.
Ramadhan DS, Siharis F, Abdurrahman S, Isrul M, Fakih TM. 2021. In silico analysis of marine natural product from sponge (Clathria Sp.) for their activity as inhibitor of SARS-CoV-2 Main Protease. Journal of Biomolecular Structure and Dynamics. vol 23: 1–7. doi: https://doi.org/10.1080/07391102.2021.1959405.
Rotondi M, Coperchini F, Ricci G, Denegri M, Croce L, Ngnitejeu ST, Villani L, Magri F, Latrofa F, Chiovato L. 2021. Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis. Journal of Endocrinological Investigation. vol 44(5): 1085–1090. doi: https://doi.org/10.1007/s40618-020-01436-w.
Sasidharan S, Selvaraj C, Singh SK, Dubey VK, Kumar S, Fialho AM, Saudagar P. 2020. Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics. vol 39(15): 1–6. doi: https://doi.org/10.1080/07391102.2020.1787864.
Schneidman-Duhovny D, Inbar Y, Nussinov R, Wolfson HJ. 2005. PatchDock and SymmDock: servers for rigid and symmetric docking. Nucleic Acids Research. vol 33(2): 363–367. doi: https://doi.org/10.1093/nar/gki481.
Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. 2020. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research. vol 24: 91–98. doi: https://dx.doi.org/10.1016%2Fj.jare.2020.03.005.
Tomic N, Pojskic L, Kalajdzic A, Ramic J, Kadric NL, Ikanovic T, Maksimovic M, Pojskic N. 2020. Screening of preferential binding affinity of selected natural compounds to SARS-CoV-2 proteins using in silico methods. EJMO. vol 4(4): 319–323. doi: https://doi.org/10.14744/ejmo.2020.72548.
Verma D, Mitra D, Paul M, Chaudhary P, Kamboj A, Thatoi H, Janmeda P, Jain D, Panneerselvam P, Shrivastav R, Pant K, Mohapatra PKD. 2021. Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/3CLpro: molecular docking and simulation studies of three pertinent medicinal plant natural components. Current Research in Pharmacology and Drug Discovery. vol 2: 1–23. doi: https://doi.org/10.1016/j.crphar.2021.100038.
Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. 2020. COVID-19: what has been learned and to be learned about the novel coronavirus disease. International Journal of Biological Sciences. vol 16(10): 1753–1766. doi: https://dx.doi.org/10.7150%2Fijbs.45134.
Yao TT, Qian JD, Zhu WY, Wang Y, Wang GQ. 2020. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus—A possible reference for coronavirus disease‐19 treatment option. Journal of medical virology. vol 92(6): 556–563. doi: https://doi.org/10.1002/jmv.25729.
Zhang Q, Xiang R, Huo S, Zhou Y, Jiang S, Wang Q, Yu F. 2021. Molecular mechanism of interaction between SARS-CoV-2 and host cells and interventional therapy. Signal Transduction and Targeted Therapy. vol 6(1): 1–9. doi: https://doi.org/10.1038/s41392-021-00653-w.
Zheng J. 2020. SARS-CoV-2: an emerging coronavirus that causes a global threat. International Journal of Biological Sciences. vol 16(10): 1–8. doi: https://dx.doi.org/10.7150%2Fijbs.45053.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. 2020. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 579(7798): 270–273. doi: https://doi.org/10.1038/s41586-020-2012-7.
Copyright (c) 2021 Taufik Muhammad Fakih, Dwi Syah Fitra Ramadhan
This work is licensed under a Creative Commons Attribution 4.0 International License.
COPYRIGHT AND LICENSE STATEMENT
Biogenesis: Jurnal Ilmiah Biologi is published under the terms of the Creative Commons Attribution license. Authors hold the copyright and retain publishing rights without restriction to their work. Users may read, download, copy, distribute, and print the work in any medium, provided the original work is properly cited.
LICENSE TO PUBLISH
The use of the article will be governed by the Creative Commons Attribution license as currently displayed on http://creativecommons.org/licenses/by/4.0.
2. Author’s Warranties
The author warrants that the article is original, written by stated author/s, has not been published before, contains no unlawful statements, does not infringe the rights of others, is subject to copyright that is vested exclusively in the author and free of any third party rights, and that any necessary written permissions to quote from other sources have been obtained by the author(s).
3. User Rights
Under the Creative Commons Attribution license, the users are free to download, reuse, reprint, modify, distribute and/or copy the content for any purpose, even commercially, as long as the original authors and source are cited. No permission is required from the authors or the publishers.
If the article was prepared jointly with other authors, the corresponding author warrants that he/she has been authorized by all co-authors, and agrees to inform his/her co-authors of the terms of this statement.
Biogenesis: Jurnal Ilmiah Biologi may conform the article to a style of punctuation, spelling, capitalization, and usage that it deems appropriate. The author acknowledges that the article may be published so that it will be publicly accessible and such access will be free of charge for the readers.