Papain-like Protease Peptides as Construction Material for the SARS-CoV-2 Vaccine Design Candidate: In-silico Study
DOI:
https://doi.org/10.15408/jkv.v11i1.42748Keywords:
Bioinformatics, COVID-19, immunoinformatic, papain-like protease, vaccine designAbstract
COVID-19 remains a major global health threat. In addition to implementing health protocols and consuming supplements, proactive prevention strategies are essential to limit the spread of the virus. One of the most promising approaches is the use of vaccines, particularly peptide-based vaccines, which are under active development. This study aimed to design a peptide vaccine derived from the SARS-CoV-2 papain-like protease (PLpro) and evaluate its interaction with key components of the human immune system, namely Toll-like receptor 3 (TLR3), major histocompatibility complex class I (MHC-I), and class II (MHC-II). The research employed an immunoinformatics approach utilizing NetCTL, IEDB Tepitool, PEP-FOLD3, trRosetta, HDOCK, GalaxyRefine2, and other molecular modeling tools. The designed vaccine construct was visualized in 3D using trRosetta and validated through ERRAT2, achieving a 100% quality score, indicating excellent structural integrity. The docking simulations demonstrated stable interactions between the vaccine and the immune receptors, suggesting strong immunogenic potential. In conclusion, the in silico-designed peptide vaccine based on SARS-CoV-2 PLpro shows promise in triggering immune responses through stable binding with TLR3, MHC-I, and MHC-II, highlighting its potential as a candidate for further experimental validation in COVID-19 vaccine development.
Downloads
References
1. Aditia A. COVID-19 : Epidemiologi, Virologi, Penularan, Gejala Klinis, Diagnosa, Tatalaksana, Faktor Risiko Dan Pecegahan. Jurnal Penelitian Perawat Profesional. 2021;3(4):653-660. Accessed January 19, 2023. https://jurnal.globalhealthsciencegroup.com/index.php/JPPP/article/view/574/410
2. World Health Organization. WHO Coronavirus (COVID-19) Dashboard. World Health Organization. February 16, 2023. Accessed August 30, 2023. https://covid19.who.int/
3. Kemkes RI. COVID-19. Kementrian Kesehatan RI. January 18, 2023. Accessed August 30, 2023. https://infeksiemerging.kemkes.go.id/dashboard/covid-19
4. Lukito JI. Tinjauan Antivirus untuk Terapi COVID-19. CDK-286. 2020;47(5):340-345. Accessed January 19, 2023. http://download.garuda.kemdikbud.go.id/article.php?article=2468337&val=23521&title=Tinjauan%20 Antivirus%20untuk%20Terapi%20COVID-19
5. Pisoschi AM, Pop A, Iordache F, et al. Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Europian Journal of Medicinal Chemistry. 2022;232:1-24. doi: https://doi.org/10.1016 /j.ejmech.2022.114175
6. Dong Y, Dai T, Wei Y, Zhang L, Zheng M, Zhou F. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduct Target Ther. 2020;5:1-14. doi: . https://doi.org/10.1038/s41392-020-00352-y
7. Rezaldi F, Taupiqurrohman O, Fadillah MF, Rochmat A, Humaedi A, Fadhilah F. Identifikasi Kandidat Vaksin COVID-19 Berbasis Peptida dari Glikoprotein Spike SARS CoV-2 untuk Ras Asia secara In Silico. Jurnal Biotek Medisiana Indonesia . 2021;10(1):77-85. Accessed January 19, 2023. https://ejournal2.litbang.kemkes.go.id /index.php/jbmi/article/view/5031/2299
8. Syakuran L ’Abdan. Desain Kandidat Vaksin SARS-CoV-2 Menggunakan Pendekatan Imunoinformatika. ResearchGate. Published online August 26, 2020:1-11. doi:https://doi.org/10.13140/RG.2.2.33453.31202
9. Naveed M, Tehreem S, Arshad S, et al. Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains. J Infect Public Health. 2021;14(7):938-946. doi: https://doi.org/10.1016/j.jiph.2021.04.010
10. Islam MdJ, Islam NN, Alom MdS, Kabir M, Halim MA. A Review on Structural, Non-structural, and Accessory Proteins of SARS-CoV-2: Highlighting Drug Target Sites. Immunobiology. Published online January 2023:1-24. doi: https://doi.org/10.1016/j.imbio.2022.152302
11. Firmansyah MA, Susilo A, Haryanti SD, Herowati R. Desain Vaksin Berbasis Epitop dengan Pendekatan Bioinformatika untuk Menekan Glikoprotein Spike SARS-CoV-2. Jurnal Farmasi Indonesia. 2021;18(2):82-96. Accessed January 19, 2023. http://ejurnal.setiabudi.ac.id/ojs/index.php/farmasi-indonesia/article/view/1351/809
12. Ruswanto. Desain Dan Studi Interaksi senyawa N’-(3,5-Dinitrobenzoyl)-Isonicotinohydrazide pada Mycobacterium Tuberculosis Enoyl-Acyl Carrier Protein Reductase (INHA). Jurnal Kesehatan Bakti Tunas Husada. 2014;12(1):192-201. Accessed January 19, 2023. https://ejurnal.universitas-bth.ac.id/index.php/ P3M_JKBTH/article/view/79/79.
13. Septian AD, Wardani GA, Mardianingrum R, Ruswanto R. The Virtual Screening of Flavonoid Derivatives on Progesterone, Estrogen, and HER-2 Receptor for Breast Cancer Treatment Candidate. Jurnal Kimia Valensi. 2023 Jun 28;9(1):163-82.
14. Mardianingrum R, Susilawati D, Ruswanto R. Computational Study of 1-(3-Nitrobenzoyloxymethyl)-5-Fluorouracil Derivatives as Colorectal Cancer Agents. Jurnal Kimia Valensi. 2022 Nov 24;8(2):211-20.
15. Badrunanto B, Asoka SF, Wahyuni WT, Farid M, Wahyudi ST, Batubara I. Component Discrimination and Anti-skin-aging Potency of Emprit and Red Ginger Essential Oil: Chemometric, Molecular Docking and Molecular Dynamics Study. Jurnal Kimia Valensi. 2023 Dec 15;9(2):183-94.
16. Khairkhah N, Aghasadeghi MR, Namvar A, Bolhassani A. Design of novel multiepitope constructs-based peptide vaccine against the structural S, N and M proteins of human COVID-19 using immunoinformatics analysis. PLoS One. 2020;15(10):1-28. doi:https://doi.org/10.1371/journal. pone.0240577
17. Bibi S, Ullah I, Zhu B, et al. In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology. Sci Rep. 2021;11(1):1-16. doi: https://doi.org/10.1038/s41598-020-80899-6
18. RCSB PDB. (2023, July 1). Resolution. RCSB PDB-101. https://pdb101.rcsb.org/learn/guide-to-understanding-pdb-data/crystallographic-data
19. NCBI. Glossary. National Library of Medicine. 2023. Accessed August 31, 2023. https://www.ncbi.nlm.nih.gov/books/NBK470040/
20. Syngai G, Barman P, Bharali R, Dey S. BLAST: An introductory tool for students to Bioinformatics Applications. Keanean Journal of Science. 2013;2:67-76. https://www.researchgate.net/publication/267332265
21. Anwar M, Nurjanah S, Rahayu WP. Aplikasi Basic Local Alignment Search Tool (Blast) NCBI Pada Penelitian Molekuler Salmonella SPP. Syntax Literate: Jurnal Ilmiah Indonesia. 2022;7(11):15446-15464. Accessed July 7, 2023. https://doi.org/10.36418/syntax-literate.v7i10
22. Russo CA de M, Selvatti AP. Bootstrap and rogue identification tests for phylogenetic analyses. Molecular Biology and Evolution, 35(9), 2327–2333. https://doi.org/10.1093/molbev/msy118.
23. Eernisse DJ. Introduction to Phylogeny: What is a Sister Taxon? Biology 404 - Evolution. 2023. Accessed August 31, 2023. http://biology.fullerton.edu/biol404/phylo/sisters.html
24. Rawal, K., Sinha, R., Abbasi, B. A., Chaudhary, A., Nath, S. K., Kumari, P., Preeti, P., Saraf, D., Singh, S., Mishra, K., Gupta, P., Mishra, A., Sharma, T., Gupta, S., Singh, P., Sood, S., Subramani, P., Dubey, A. K., Strych, U., … Bottazzi, M. E. (2021). Identification of vaccine targets in pathogens and design of a vaccine using computational approaches. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-96863-x.22
25. NetCTL. (2023, July 1). NetCTL - 1.2 Predection of CTL epitopes in protein sequences. DTU Health Tech. https:// services.healthtech.dtu.dk/service.php?NetCTL-1.2.
26. IEDBAR. (2023, July 1). IEDB Analysis Resource. IEDBAR. http://tools.iedb.org/main/
27. Ong E, He Y, Yang Z. Epitope promiscuity and population coverage of Mycobacterium tuberculosis protein antigens in current subunit vaccines under development. Infection, Genetics and Evolution. 2020;80:1-6. doi: https://doi.org/10.1016/j.meegid.2020.104186
28. Kar, T., Narsaria, U., Basak, S., Deb, D., Castiglione, F., Mueller, D. M., & Srivastava, A. P. (2020). A candidate multi-epitope vaccine against SARS-CoV-2. Scientific Reports, 10(1), 10895. https://doi.org/10.1038/s41598-020-67749-1.
29. Qamar MT ul, Rehman A, Tusleem K, et al. Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches. PLOS ONE. 2020;15(12):1-25. doi: https://doi.org/10.1371/journal. pone.0244176.
30. Mulyani S, Egel E, Kittel C, Turkanovic S, Wohlleben W, Süssmuth RD, van Pée KH. The Thioesterase Bhp is Involved in the Formation of β‐Hydroxytyrosine during Balhimycin Biosynthesis in Amycolatopsis balhimycina. ChemBioChem. 2010 Jan 25;11(2):266-71.
31. Sanami, S., Alizadeh, M., Nosrati, M., Dehkordi, K. A., Azadegan-Dehkordi, F., Tahmasebian, S., Nosrati, H., Arjmand, M. H., Ghasemi-Dehnoo, M., Rafiei, A., & Bagheri, N. (2021). Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study. Computers in Biology and Medicine, 133. https://doi.org/10.1016/j.compbiomed.2021.104390
32. Walker JM, Gasteiger E, Hoogland C, et al. The Proteomics Protocols Handbook Edited Protein Identification and Analysis Tools on the ExPASy Server. (Walker J, ed.). Springer Science & Business Media; 2005. http://www.expasy.org/tools/
33. Renadi S, Pratita ATK, Mardianingrum R, Ruswanto R. The Potency of Alkaloid Derivates as Anti-Breast Cancer Candidates: In Silico Study. Jurnal Kimia Valensi. 2023;9(1):89-108. doi: https://doi.org/10.15408/jkv.v9i1. 31481
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Richa Mardianingrum, Nur Ihsani Pertiwi, Lina Rahmawati Rizkuloh, Ruswanto Ruswanto
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
