Abstract
An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate.
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References
Babkin, I. V, Babkina, I. N., & Tikunova, N. V. (2022). An Update of Orthopoxvirus Molecular Evolution. Viruses, 14(2):388. https://doi.org/10.3390/v14020388
Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81(8):3684–3690. https://doi.org/10.1063/1.448118
Case D, Ben-Shalom I, Brozell SR, Cerutti DS, Cheatham T, Cruzeiro V WD, Darden T, Duke R, Ghoreishi D, Gilson M, Gohlke H, Götz A, Greene D, Harris R, Homeyer N, Huang Y, Izadi S, Kovalenko A, Kurtzman T, Kollman PA (2018) Amber 2018. https://doi.org/10.13140/RG.2.2.31525.68321
Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N⋅log(N) method for Ewald sums in large systems. J Chem Phys 98(12):10089–10092. https://doi.org/10.1063/1.464397
Doytchinova IA, Flower DR (2007) VaxiJen : a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform 8(1):4. https://doi.org/10.1186/1471-2105-8-4
El-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B-cell epitopes using string kernels. J Mol Recognit 21(4):243–255. https://doi.org/10.1002/jmr.893
Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, Bairoch A (2003) ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 31(13):3784–3788. https://doi.org/10.1093/nar/gkg563
Gohlke H, Case DA (2004) Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf. J Comput Chem 25(2):238–250. https://doi.org/10.1002/jcc.10379
Gohlke H, Kiel C, Case DA (2003) Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras-RalGDS complexes. J Mol Biol 330(4):891–913. https://doi.org/10.1016/s0022-2836(03)00610-7
Jonniya NA, Sk MF, Kar P (2022) A comparative study of structural and conformational properties of WNK kinase isoforms bound to an inhibitor: insights from molecular dynamic simulations. J Biomol Struct Dyn 40(3):1400–1415. https://doi.org/10.1080/07391102.2020.1827035
Joshi A, Sasumana J, Ray NM, Kaushik V (2021) Neural network analysis. In: Singh V, Kumar A (eds) Advances in bioinformatics. Springer Singapore, Singapore, pp 351–364. https://doi.org/10.1007/978-981-33-6191-1_18
Joshi A, Ray NM, Singh J, Upadhyay AK, Kaushik V (2022) T-cell epitope-based vaccine designing against Orthohantavirus: a causative agent of deadly cardio-pulmonary disease. Netw Model Anal Health Inform Bioinform 11(1):1–10. https://doi.org/10.1007/s13721-021-00339-x
Joshi A, Akhtar N, Sharma NR, Kaushik V, Borkotoky S (2023) MERS virus spike protein HTL-epitopes selection and multi-epitope vaccine design using computational biology. J Biomol Struct Dyn 41(22):12464–12479. https://doi.org/10.1080/07391102.2023.2191137
Jung D, Jeong SK, Lee CM, Noh KT, Heo DR, Shin YK, Yun CH, Koh WJ, Akira S, Whang J, Kim HJ, Park WS, Shin SJ, Park YM (2011) Enhanced efficacy of therapeutic cancer vaccines produced by Co-treatment with mycobacterium tuberculosis heparin-binding hemagglutinin, a novel TLR4 agonist. Can Res 71(8):2858–2870. https://doi.org/10.1158/0008-5472.CAN-10-3487
Kaler J, Hussain A, Flores G, Kheiri S, Desrosiers D (2022) Monkeypox: a comprehensive review of transmission, pathogenesis, and manifestation. Cureus 14(7):1–11. https://doi.org/10.7759/cureus.26531
Kollman PA, Massova I, Reyes C, Kuhn B, Huo S, Chong L, Lee M, Lee T, Duan Y, Wang W, Donini O, Cieplak P, Srinivasan J, Case DA, Cheatham TE 3rd (2000) Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc Chem Res 33(12):889–897. https://doi.org/10.1021/ar000033j
Kozakov D, Beglov D, Bohnuud T, Mottarella SE, Xia B, Hall DR, Vajda S (2013) How good is automated protein docking? Proteins 81(12):2159–2166. https://doi.org/10.1002/prot.24403
Kräutler V, Van Gunsteren WF, Hünenberger PH (2001) A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations. J Comput Chem 22(5):501–508. https://doi.org/10.1002/1096-987X(20010415)22:5%3c501::AID-JCC1021%3e3.0.CO;2-V
Krishnan GS, Joshi A, Akhtar N, Kaushik V (2021) Immunoinformatics designed T cell multi epitope dengue peptide vaccine derived from non structural proteome. Microbial Pathog 150(December 2020):104728. https://doi.org/10.1016/j.micpath.2020.104728
Lai CC, Hsu CK, Yen MY, Lee PI, Ko WC, Hsueh PR (2022) Monkeypox: an emerging global threat during the COVID-19 pandemic. J Microbiol Immunol Infect 55(5):787–794. https://doi.org/10.1016/j.jmii.2022.07.004
Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26(2):283–291. https://doi.org/10.1107/s0021889892009944
Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C (2015) ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput 11(8):3696–3713. https://doi.org/10.1021/acs.jctc.5b00255
Masulli F, Mitra S (2009) Natural computing methods in bioinformatics: a survey. Inf Fusion 10(3):211–216. https://doi.org/10.1016/j.inffus.2008.12.002
Miller BR, McGee TDJ, Swails JM, Homeyer N, Gohlke H, Roitberg AE (2012) MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput 8(9):3314–3321. https://doi.org/10.1021/ct300418h
Naveed M, Ahmed I, Khalid N, Mumtaz AS (2014a) Bioinformatics based structural characterization of glucose dehydrogenase (gdh) gene and growth promoting activity of Leclercia sp. QAU-66. Braz J Microbiol 45(2):603–611. https://doi.org/10.1590/s1517-83822014000200031
Naveed M, Mubeen S, Khan S, Ahmed I, Khalid N, Suleria HAR, Bano A, Mumtaz AS (2014b) Identification and characterization of rhizospheric microbial diversity by 16S ribosomal RNA gene sequencing. Braz J Microbiol 45(3):985–993. https://doi.org/10.1590/s1517-83822014000300031
Naveed M, Tehreem S, Mubeen S, Nadeem F, Zafar F, Irshad M (2016) In-silico analysis of non-synonymous-SNPs of STEAP2: to provoke the progression of prostate cancer. Open Life Sci 11(1):402–416. https://doi.org/10.1515/biol-2016-0054
Nezafat N, Ghasemi Y, Javadi G, Khoshnoud MJ, Omidinia E (2014) A novel multi-epitope peptide vaccine against cancer: an in silico approach. J Theor Biol 349:121–134. https://doi.org/10.1016/j.jtbi.2014.01.018
Pandey RK, Bhatt TK, Prajapati VK (2018) Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating anopheles salivary protein. Sci Rep 8(1):1–11. https://doi.org/10.1038/s41598-018-19456-1
Pandya N, Kumar A (2023) Immunoinformatics analysis for design of multi-epitope subunit vaccine by using heat shock proteins against Schistosoma mansoni. J Biomol Struct Dyn 41(5):1859–1878. https://doi.org/10.1080/07391102.2021.2025430
Pastor RW, Brooks BR, Szabo A (1988) An analysis of the accuracy of Langevin and molecular dynamics algorithms. Mol Phys 65(6):1409–1419. https://doi.org/10.1080/00268978800101881
Petersen E, Kantele A, Koopmans M, Asogun D, Yinka-Ogunleye A, Ihekweazu C, Zumla A (2019) Human Monkeypox: epidemiologic and clinical characteristics, diagnosis, and prevention. Infect Dis Clin North Am 33(4):1027–1043. https://doi.org/10.1016/j.idc.2019.03.001
Price DJ, Brooks CL 3rd (2004) A modified TIP3P water potential for simulation with Ewald summation. J Chem Phys 121(20):10096–10103. https://doi.org/10.1063/1.1808117
Rapin N, Lund O, Bernaschi M, Castiglione F (2010) Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PLoS ONE. https://doi.org/10.1371/journal.pone.0009862
Reynisson B, Alvarez B, Paul S, Peters B, Nielsen M (2021) NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res 48(W1):449–454. https://doi.org/10.1093/NAR/GKAA379
Roe DR, Cheatham TE (2013) PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput 9(7):3084–3095. https://doi.org/10.1021/ct400341p
Sami SA, Marma KKS, Mahmud S, Khan MAN, Albogami S, El-Shehawi AM, Rakib A, Chakraborty A, Mohiuddin M, Dhama K, Uddin MMN, Hossain MK, Tallei TE, Emran TB (2021) Designing of a multi-epitope vaccine against the structural proteins of marburg virus exploiting the immunoinformatics approach. ACS Omega 6(47):32043–32071. https://doi.org/10.1021/acsomega.1c04817
Shantier SW, Mustafa MI, Abdelmoneim AH, Fadl HA, Elbager SG, Makhawi AM (2022) Novel multi epitope-based vaccine against monkeypox virus: vaccinomic approach. Sci Rep 12(1):1–17. https://doi.org/10.1038/s41598-022-20397-z
Shchelkunova GA, Shchelkunov SN (2022) Smallpox, Monkeypox and other human orthopoxvirus infections. Viruses 15(1):103. https://doi.org/10.3390/v15010103
Sk MF, Kar P (2022) Finding inhibitors and deciphering inhibitor-induced conformational plasticity in the Janus kinase via multiscale simulations. SAR QSAR Environ Res 33(11):833–859. https://doi.org/10.1080/1062936X.2022.2145352
Sk MF, Roy R, Jonniya NA, Poddar S, Kar P (2021) Elucidating biophysical basis of binding of inhibitors to SARS-CoV-2 main protease by using molecular dynamics simulations and free energy calculations. J Biomol Struct Dyn 39(10):3649–3661. https://doi.org/10.1080/07391102.2020.1768149
Sk MF, Jonniya NA, Roy R, Kar P (2022) Unraveling the molecular mechanism of recognition of selected next-generation antirheumatoid arthritis inhibitors by Janus Kinase 1. ACS Omega 7(7):6195–6209. https://doi.org/10.1021/acsomega.1c06715
Xue LC, Rodrigues JP, Kastritis PL, Bonvin AM, Vangone A (2016) PRODIGY: a web server for predicting the binding affinity of protein-protein complexes. Bioinformatics (oxford, England) 32(23):3676–3678. https://doi.org/10.1093/bioinformatics/btw514
Acknowledgements
The authors would like to acknowledge Prof. Amit Kumar and Dr. Parimal Kar for the computer server facility at IIT, Indore. AN would like to acknowledge the Council of Scientific & Industrial Research (CSIR), Govt. of India, New Delhi, AC, and NK to Department of Biotechnology, SS and SS to Ministry of Human Resource Development, Govt. of India, New Delhi for their individual fellowship.
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Nayak, A.K., Chakraborty, A., Shukla, S. et al. An immunoinformatic approach for developing a multi-epitope subunit vaccine against Monkeypox virus. In Silico Pharmacol. 12, 42 (2024). https://doi.org/10.1007/s40203-024-00220-5
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DOI: https://doi.org/10.1007/s40203-024-00220-5