In silico multi-epitope Bunyumwera virus vaccine to target virus nucleocapsid N protein

Kanaka Durga Devi Nelluri1, Manne Anupama Ammulu2, M. Lakshmi Durga1, Melika Sravani1, Vemuri Praveen Kumar3, Sudhakar Poda4
1Department of Pharmaceutics and Biotechnology, KVSR Siddhartha College of Pharmaceutical Sciences, Vijayawada, India
2Department of Civil Engineering, PVP Siddhartha Institute of Technology, Kanuru, Vijayawada, India
3Department of Biotechnology, Koneru Lakshmaiah University, Vaddeswaram, India
4Department of Biotechnology, Acharya Nagarjuna University, Guntur, India

Tóm tắt

Bunyumwera virus can cause 82% mortality in humans currently with no vaccine or drugs for treatment. We described an in silico multi-epitope vaccine targeting Bunyumwera virus nucleocapsid N-protein and predicted B and T cell epitopes for immunogenicity, allergenicity, toxicity, and conservancy. For creating the most potent immunological response possible, docking epitopes with HLA alleles are chosen to screen them. The 3D vaccination was docked with the Toll-like receptor-8 using molecular dynamic simulations. To ensure production efficiency, the vaccine sequence was further cloned in silico in a plasmid pIB2 vector. For efficacy and safety, results must be supported in vitro and in vivo. The vaccine was cloned to enable expression and translation in a plasmid vector pIB2. It was expected to be antigenic, non-allergenic, and have a high binding affinity with TLR-8 in silico cloning. This multi-epitope vaccination may stimulate both innate and adaptive immunity. The vaccine developed in this work was based on the nucleocapsid N-protein of the Bunyumwera virus and was created using a reverse vaccinology method. Further experimental validation is required to assess the vaccine’s therapeutic effectiveness and immunogenicity.

Tài liệu tham khảo

Burrell CJ (2017) Chapter-29: Bunyaviruses, in Fenner and White’s Medical. Virology: 407–424 Fausta Dutuze M, Nzayirambaho M, Mores CN, Christofferson RC (2018) A review of Bunyamwera, Batai, and Ngari viruses: understudied orthobunyaviruses with potential one health implications. Front. Vet. Sci 5, no. APR:1–9. https://doi.org/10.3389/fvets.2018.00069 Li B et al (2013) Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation. Proc. Natl. Acad. Sci. U. S. A 110(22):9048–9053. https://doi.org/10.1073/pnas.1222552110 Doytchinova IA, Flower DR (2007) VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 8:1–7. https://doi.org/10.1186/1471-2105-8-4 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 Larsen MV, Lundegaard C, Lamberth K, Buus S, Lund O, Nielsen M (2007) Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinformatics 8:1–12. https://doi.org/10.1186/1471-2105-8-424 Zhao JW, Yan M, Shi G, Zhang SL, Ming L (2017) In silico identification of cytotoxic T lymphocyte epitopes encoded by RD5 region of Mycobacterium tuberculosis. J. Infect. Dev. Ctries. 11(10):806–810. https://doi.org/10.3855/jidc.7207 Chauhan V, Goyal K, Singh MP (2018) Identification of broadly reactive epitopes targeting major glycoproteins of Herpes simplex virus (HSV) 1 and 2 - an immunoinformatics analysis. Infect. Genet. Evol. 61:24–35. https://doi.org/10.1016/j.meegid.2018.03.004 Dimitrov I, Bangov I, Flower DR, Doytchinova I (2014) AllerTOP v.2 - a server for in silico prediction of allergens. J. Mol. Model 20(6). https://doi.org/10.1007/s00894-014-2278-5 Bui HH, Sidney J, Li W, Fusseder N, Sette A (2007) Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines. BMC Bioinformatics 8:1–6. https://doi.org/10.1186/1471-2105-8-361 Tian W, Chen C, Lei X, Zhao J, Liang J (2018) CASTp 3.0: Computed atlas of surface topography of proteins. Nucleic Acids Res 46(W1):W363–W367. https://doi.org/10.1093/nar/gky473 Mugilan A et al (2010) In silico secondary structure prediction method (Kalasalingam University Structure Prediction Method) using comparative analysis. Trends Bioinforma 3(1):11–19 Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE (2015) Europe PMC Funders Group The Phyre2 web portal for protein modelling, prediction and analysis. Nat. Protoc 10(6):845–858. https://doi.org/10.1038/nprot.2015.053.The Colovos C, Yeates TO (1993) Verification of protein structures: patterns of nonbonded atomic interactions. Protein Sci 2(9):1511–1519. https://doi.org/10.1002/pro.5560020916 Bowie JU et al (1991) A method to identify protein sequences that fold into a known three-dimensional structure. Science 80:164–170 Carugo O, Djinovic Carugo K (2013) Half a century of Ramachandran plots, Acta Crystallogr. Sect. D Biol. Crystallogr 69(8):1333–1341. https://doi.org/10.1107/S090744491301158X Sandra N. Lester and Kui Li, Toll-like receptors in antiviral innate immunity, J. Mol. Biol., no. January, 2013. Eyal E, Lum G, Bahar I (2015) The anisotropic network model web server at 2015 (ANM 2.0). Bioinformatics 31(9):1487–1489. https://doi.org/10.1093/bioinformatics/btu847