{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:28:46Z","timestamp":1772252926691,"version":"3.50.1"},"reference-count":107,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019), as a global pandemic. Additionally, the positive cases are still following an upward trend worldwide and as a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication and interferes with host immune responses. We comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we predicted the most immunogenic epitope for the T-cell and B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.<\/jats:p>","DOI":"10.3390\/molecules25215088","type":"journal-article","created":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T19:51:31Z","timestamp":1604346691000},"page":"5088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Epitope-Based Immunoinformatics Approach on Nucleocapsid Protein of Severe Acute Respiratory Syndrome-Coronavirus-2"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-0368","authenticated-orcid":false,"given":"Ahmed","family":"Rakib","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0621-4523","authenticated-orcid":false,"given":"Saad Ahmed","family":"Sami","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. Ashiqul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"},{"name":"Department of Pharmacy, Mawlana Bhashani Science &amp; Technology University, Santosh, Tangail 1902, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahriar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhana Binta","family":"Faiz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibi Humayra","family":"Khanam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay Kay Shain","family":"Marma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maksuda","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mir Muhammad Nasir","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Biological Sciences, University of Chittagong, Chittagong 4331, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-4023","authenticated-orcid":false,"given":"Firzan","family":"Nainu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Hasanuddin University, Tamalanrea, Kota Makassar, Sulawesi Selatan 90245, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-9737","authenticated-orcid":false,"given":"Jesus","family":"Simal-Gandara","sequence":"additional","affiliation":[{"name":"Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo\u2013Ourense Campus, E32004 Ourense, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus--infected pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"Jama"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early transmission dynamics in Wuhan, China, of novel coronavirus\u2013infected pneumonia","volume":"382","author":"Li","year":"2020","journal-title":"N. Eng. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gralinski, L.E., and Menachery, V.D. (2020). Return of the Coronavirus: 2019-nCoV. Viruses, 12.","DOI":"10.3390\/v12020135"},{"key":"ref_4","unstructured":"World Health Organization (2020). Coronavirus Disease 2019 (COVID-19): Situation Report, World Health Organization."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/S0140-6736(20)30154-9","article-title":"A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster","volume":"395","author":"Chan","year":"2020","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/22221751.2020.1719902","article-title":"Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan","volume":"9","author":"Chan","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wu, F., Zhao, S., Yu, B., Chen, Y.-M., Wang, W., Hu, Y., Song, Z.-G., Tao, Z.-W., Tian, J.-H., and Pei, Y.-Y. (2020). Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China. bioRxiv.","DOI":"10.1101\/2020.01.24.919183"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.virusres.2007.10.009","article-title":"SARS coronavirus accessory proteins","volume":"133","author":"Narayanan","year":"2008","journal-title":"Virus Res."},{"key":"ref_11","first-page":"11","article-title":"Vaccine and antibody-directed T cell tumour immunotherapy","volume":"1704","author":"Dermime","year":"2004","journal-title":"Biochim. Biophys. Acta BBA-Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1006\/biol.2001.0298","article-title":"Synthetic peptide vaccines: Unexpected fulfillment of discarded hope?","volume":"29","author":"Meloen","year":"2001","journal-title":"Biologicals"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11034","DOI":"10.1128\/JVI.01505-14","article-title":"Virus-specific memory CD8 T cells provide substantial protection from lethal severe acute respiratory syndrome coronavirus infection","volume":"88","author":"Channappanavar","year":"2014","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eaaw2888","DOI":"10.1126\/scitranslmed.aaw2888","article-title":"Vaccines and global health: In search of a sustainable model for vaccine development and delivery","volume":"11","author":"Rappuoli","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4931","DOI":"10.1016\/j.vaccine.2007.03.049","article-title":"Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6\/11\/16\/18 L1 virus-like particle (VLP) vaccine","volume":"25","author":"Olsson","year":"2007","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0145-305X(99)00078-6","article-title":"Immunology of avian influenza virus: A review","volume":"24","author":"Suarez","year":"2000","journal-title":"Dev. Comp. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1016\/j.cell.2016.08.005","article-title":"Tailored immunogens direct affinity maturation toward HIV neutralizing antibodies","volume":"166","author":"Briney","year":"2016","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Pedersen, S.R., Christensen, J.P., Buus, S., Rasmussen, M., Korsholm, K.S., Nielsen, M., and Claesson, M.H. (2016). Immunogenicity of HLA class I and II double restricted influenza A-derived peptides. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0145629"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/sj.cr.7290158","article-title":"Identification of an epitope of SARS-coronavirus nucleocapsid protein","volume":"13","author":"Ying","year":"2003","journal-title":"Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103967","DOI":"10.1016\/j.compbiomed.2020.103967","article-title":"Immunoinformatics-guided design of an epitope-based vaccine against severe acute respiratory syndrome coronavirus 2 spike glycoprotein","volume":"124","author":"Rakib","year":"2020","journal-title":"Comput. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"999","DOI":"10.22207\/JPAM.14.SPL1.38","article-title":"Construction of epitope-based peptide vaccine against SARS-CoV-2: Immunoinformatics study","volume":"14","author":"Kharisma","year":"2020","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.virol.2006.03.036","article-title":"Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients","volume":"351","author":"Peng","year":"2006","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0378-1135(00)00202-9","article-title":"Localization of linear B-cell epitopes on infectious bronchitis virus nucleocapsid protein","volume":"75","author":"Seah","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41421-020-0153-3","article-title":"Network-based drug repurposing for novel coronavirus 2019-nCoV\/SARS-CoV-2","volume":"6","author":"Zhou","year":"2020","journal-title":"Cell Discov."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104497","DOI":"10.1016\/j.meegid.2020.104497","article-title":"Repurposing of SARS-CoV nucleocapsid protein specific nuclease resistant RNA aptamer for therapeutics against SARS-CoV-2","volume":"85","author":"Parashar","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3389\/fimmu.2019.00113","article-title":"Comparison of open-source reverse vaccinology programs for bacterial vaccine antigen discovery","volume":"10","author":"Dalsass","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/bioinformatics\/11.6.681","article-title":"SOPMA: Significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments","volume":"11","author":"Geourjon","year":"1995","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"W526","DOI":"10.1093\/nar\/gkh468","article-title":"Protein structure prediction and analysis using the Robetta server","volume":"32","author":"Kim","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Dimitrov, I., Flower, D.R., and Doytchinova, I. (2013). AllerTOP-a server for in silico prediction of allergens. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-S6-S4"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"Saha","year":"2006","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"taaa021","DOI":"10.1093\/jtm\/taaa021","article-title":"The reproductive number of COVID-19 is higher compared to SARS coronavirus","volume":"27","author":"Liu","year":"2020","journal-title":"J. Travel Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1016\/S0140-6736(20)30558-4","article-title":"Comorbidities and multi-organ injuries in the treatment of COVID-19","volume":"395","author":"Wang","year":"2020","journal-title":"Lancet"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1056\/NEJMoa2001282","article-title":"A trial of lopinavir--ritonavir in adults hospitalized with severe Covid-19","volume":"382","author":"Cao","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S1473-3099(20)30141-9","article-title":"Convalescent plasma as a potential therapy for COVID-19","volume":"20","author":"Chen","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s43465-020-00183-7","article-title":"COVID-19: Current Knowledge and Best Practices for Orthopaedic Surgeons","volume":"54","author":"Chhabra","year":"2020","journal-title":"Indian J. Orthop."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2147\/DDDT.S67861","article-title":"Design of an epitope-based peptide vaccine against spike protein of human coronavirus: An in silico approach","volume":"8","author":"Oany","year":"2014","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hasan, A., Hossain, M., and Alam, J. (2013). A computational assay to design an epitope-based Peptide vaccine against Saint Louis encephalitis virus. Bioinform. Biol. Insights, 7.","DOI":"10.4137\/BBI.S13402"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3233\/ISB-2010-0435","article-title":"A computational approach for identification of epitopes in dengue virus envelope protein: A step towards designing a universal dengue vaccine targeting endemic regions","volume":"10","author":"Chakraborty","year":"2010","journal-title":"Silico Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.2217\/fvl.12.95","article-title":"A computational assay to design an epitope-based peptide vaccine against chikungunya virus","volume":"7","author":"Islam","year":"2012","journal-title":"Future Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4378","DOI":"10.1128\/jvi.71.6.4378-4384.1997","article-title":"Effect of mutations in the nucleocapsid protein (NCp7) upon Pr160 (gag-pol) and tRNA (Lys) incorporation into human immunodeficiency virus type 1","volume":"71","author":"Huang","year":"1997","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.virusres.2007.12.006","article-title":"Nucleocapsid protein function in early infection processes","volume":"134","author":"Thomas","year":"2008","journal-title":"Virus Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4638","DOI":"10.1128\/JVI.78.9.4638-4645.2004","article-title":"Generation and characterization of DNA vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus","volume":"78","author":"Kim","year":"2004","journal-title":"J. Virol."},{"key":"ref_43","first-page":"803","article-title":"Rotavirus nucleocapsid protein VP6 in vaccine compositions","volume":"13","author":"Sabara","year":"1995","journal-title":"Biotechnol. Adv."},{"key":"ref_44","first-page":"S311","article-title":"Chemical inactivation of retroviral infectivity by targeting nucleocapsid protein zinc fingers: A candidate SIV vaccine","volume":"14","author":"Arthur","year":"1998","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.virol.2004.10.016","article-title":"Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine","volume":"331","author":"Zhao","year":"2005","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1099\/vir.0.040238-0","article-title":"Mutation analysis of the cross-reactive epitopes of Japanese encephalitis virus envelope glycoprotein","volume":"93","author":"Chiou","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1039\/C7FO01558E","article-title":"Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide","volume":"9","author":"Yu","year":"2018","journal-title":"Food Funct."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Mishra, S. (2020). Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV2. ChemRxiv.","DOI":"10.26434\/chemrxiv.12253463"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1016\/j.vaccine.2008.01.057","article-title":"Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses","volume":"26","author":"Liniger","year":"2008","journal-title":"Vaccine"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Mishra, S. (2020). T cell epitope-based vaccine design for pandemic novel coronavirus 2019-nCoV. ChemRxiv.","DOI":"10.26434\/chemrxiv.12029523"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106738","DOI":"10.1016\/j.intimp.2020.106738","article-title":"Immune and bioinformatics identification of T cell and B cell epitopes in the protein structure of SARS-CoV-2: A systematic review","volume":"86","author":"Noorimotlagh","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_52","first-page":"597","article-title":"Vaccine allergy","volume":"34","author":"Caubet","year":"2014","journal-title":"Immunol. Allergy Clin."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1183\/09031936.00094306","article-title":"T-cell co-stimulatory molecules: Their role in allergic immune reactions","volume":"29","author":"Kallinich","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_54","unstructured":"Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Molecular Biology of the Cell, Garland Science."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40816-019-0127-x","article-title":"In vivo and in vitro pharmacological activities of Tacca integrifolia rhizome and investigation of possible lead compounds against breast cancer through in silico approaches","volume":"5","author":"Ahmed","year":"2019","journal-title":"Clin. Phytosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.compbiolchem.2013.03.003","article-title":"A combination of epitope prediction and molecular docking allows for good identification of MHC class I restricted T-cell epitopes","volume":"45","author":"Zhang","year":"2013","journal-title":"Comput. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1073\/pnas.1314973111","article-title":"Tuberculosis vaccine with high predicted population coverage and compatibility with modern diagnostics","volume":"111","author":"Knudsen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1365-2567.2006.02434.x","article-title":"Enhanced major histocompatibility complex class I binding and immune responses through anchor modification of the non-canonical tumour-associated mucin 1-8 peptide","volume":"119","author":"Lazoura","year":"2006","journal-title":"Immunology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.2174\/092986706777441922","article-title":"Design of peptide-based vaccines for cancer","volume":"13","author":"Pietersz","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1078\/0171-2985-00286","article-title":"Epitope-vaccine strategy against HIV-1: Today and tomorrow","volume":"208","author":"Liu","year":"2003","journal-title":"Immunobiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.tibtech.2007.12.006","article-title":"Computer-aided biotechnology: From immuno-informatics to reverse vaccinology","volume":"26","author":"Vivona","year":"2008","journal-title":"Trends Biotechnol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Larsen, M.V., Lundegaard, C., Lamberth, K., Buus, S., Lund, O., and Nielsen, M. (2007). Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-424"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.4049\/jimmunol.171.4.1741","article-title":"Identifying MHC class I epitopes by predicting the TAP transport efficiency of epitope precursors","volume":"171","author":"Peters","year":"2003","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Peters, B., and Sette, A. (2005). Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMC Bioinform., 6.","DOI":"10.1186\/1471-2105-6-132"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"145","DOI":"10.12688\/f1000research.22507.2","article-title":"In silico identification of vaccine targets for 2019-nCoV","volume":"9","author":"Lee","year":"2020","journal-title":"F1000Research"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.4049\/jimmunol.177.4.2138","article-title":"Screening and identification of severe acute respiratory syndrome-associated coronavirus-specific CTL epitopes","volume":"177","author":"Zhou","year":"2006","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s10038-020-0771-5","article-title":"Bioinformatic prediction of potential T cell epitopes for SARS-Cov-2","volume":"65","author":"Kiyotani","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1556\/amicr.61.2014.3.4","article-title":"Computational vaccinology and epitope vaccine design by immunoinformatics","volume":"61","author":"Khalili","year":"2014","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/prot.340190207","article-title":"Accuracy of protein flexibility predictions","volume":"19","author":"Vihinen","year":"1994","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3824","DOI":"10.1073\/pnas.78.6.3824","article-title":"Prediction of protein antigenic determinants from amino acid sequences","volume":"78","author":"Hopp","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4049\/jimmunol.166.1.481","article-title":"A totally synthetic polyoxime malaria vaccine containing Plasmodium falciparum B cell and universal T cell epitopes elicits immune responses in volunteers of diverse HLA types","volume":"166","author":"Nardin","year":"2001","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-40833-x","article-title":"In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases","volume":"9","author":"Shey","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.chom.2020.03.002","article-title":"A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2","volume":"27","author":"Grifoni","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102911","DOI":"10.1016\/j.ebiom.2020.102911","article-title":"Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity","volume":"58","author":"Amrun","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/jmv.1890460402","article-title":"Human B-cell epitopes of Puumala virus nucleocapsid protein, the major antigen in early serological response","volume":"46","author":"Vapalahti","year":"1995","journal-title":"J. Med. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1006\/viro.1996.0075","article-title":"Characterization of Puumala virus nucleocapsid protein: Identification of B-cell epitopes and domains involved in protective immunity","volume":"216","author":"Lundkvist","year":"1996","journal-title":"Virology"},{"key":"ref_77","first-page":"114","article-title":"Antigenic and immunogenic investigation of B-cell epitopes in the nucleocapsid protein of peste des petits ruminants virus","volume":"12","author":"Choi","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.molimm.2014.04.009","article-title":"In silico predicted mycobacterial epitope elicits in vitro T-cell responses","volume":"61","author":"Khan","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s10989-017-9617-1","article-title":"Epitope based peptide prediction from proteome of enterotoxigenic E. coli","volume":"24","author":"Khan","year":"2018","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"W509","DOI":"10.1093\/nar\/gkn202","article-title":"NetMHC-3.0: Accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8\u201311","volume":"36","author":"Lundegaard","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Flower, D.R. (2007). Immunoinformatics and the in Silico Prediction of Immunogenicity. Immunoinformatics, Springer.","DOI":"10.1007\/978-1-60327-118-9"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkn201","article-title":"NCBI BLAST: A better web interface","volume":"36","author":"Johnson","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"W580","DOI":"10.1093\/nar\/gkv279","article-title":"The EMBL-EBI bioinformatics web and programmatic tools framework","volume":"43","author":"Li","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/molbev\/mst197","article-title":"MEGA6: Molecular evolutionary genetics analysis version 6.0","volume":"30","author":"Tamura","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Doytchinova, I.A., and Flower, D.R. (2007). VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-4"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Gupta, S., Kapoor, P., Chaudhary, K., Gautam, A., Kumar, R., and Raghava, G.P.S. (2015). Peptide toxicity prediction. Computational Peptidology, Springer.","DOI":"10.1007\/978-1-4939-2285-7_7"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Laskowski, R.A., MacArthur, M.W., Moss, D.S., and Thornton, J.M. (1993). PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr.","DOI":"10.1107\/S0021889892009944"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1034\/j.1399-0039.2003.00112.x","article-title":"Sensitive quantitative predictions of peptide-MHC binding by a \u2019Query by Committee\u2019artificial neural network approach","volume":"62","author":"Buus","year":"2003","journal-title":"Tissue Antigens"},{"key":"ref_90","first-page":"30","article-title":"MHC-NP: Predicting peptides naturally processed by the MHC","volume":"400","author":"Drouin","year":"2013","journal-title":"J. Immunol. Methods"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Bui, H.-H., Sidney, J., Li, W., Fusseder, N., and Sette, A. (2007). Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-361"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nbt1215","article-title":"A consensus epitope prediction approach identifies the breadth of murine T CD8+-cell responses to vaccinia virus","volume":"24","author":"Moutaftsi","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"W498","DOI":"10.1093\/nar\/gkp323","article-title":"PEP-FOLD: An online resource for de novo peptide structure prediction","volume":"37","author":"Maupetit","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1002\/elps.1150181505","article-title":"SWISS-MODEL and the Swiss-Pdb Viewer: An environment for comparative protein modeling","volume":"18","author":"Guex","year":"1997","journal-title":"Electrophoresis"},{"key":"ref_95","unstructured":"Dallakyan, S. (2008). PyRx-python prescription v. 0.8. Scripps Res. Inst., 2010."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0959-440X(02)00344-5","article-title":"Rotamer libraries in the 21st century","volume":"12","author":"Dunbrack","year":"2002","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An open chemical toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminform."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Rakib, A., Paul, A., Chy, M.N.U., Sami, S.A., Baral, S.K., Majumder, M., Tareq, A.M., Amin, M.N., Shahriar, A., and Uddin, M.Z. (2020). Biochemical and Computational Approach of Selected Phytocompounds from Tinospora crispa in the Management of COVID-19. Molecules, 25.","DOI":"10.3390\/molecules25173936"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Jahan, I., Tona, M.R., Sharmin, S., Sayeed, M.A., Tania, F.Z., Paul, A., Chy, M.N.U., Rakib, A., Emran, T.B., and Simal-Gandara, J. (2020). GC-MS Phytochemical Profiling, Pharmacological Properties, and In Silico Studies of Chukrasia velutina Leaves: A Novel Source for Bioactive Agents. Molecules, 25.","DOI":"10.3390\/molecules25153536"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev.bi.47.070178.001343","article-title":"Empirical predictions of protein conformation","volume":"47","author":"Chou","year":"1978","journal-title":"Annu. Rev. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1128\/jvi.55.3.836-839.1985","article-title":"Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide","volume":"55","author":"Emini","year":"1985","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-5793(90)80535-Q","article-title":"A semi-empirical method for prediction of antigenic determinants on protein antigens","volume":"276","author":"Kolaskar","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/BF01195768","article-title":"Prediction of chain flexibility in proteins","volume":"72","author":"Karplus","year":"1985","journal-title":"Naturwissenschaften"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1745-7580-2-2","article-title":"Improved method for predicting linear B-cell epitopes","volume":"2","author":"Larsen","year":"2006","journal-title":"Immunome Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1546293","article-title":"Structural evidence for induced fit as a mechanism for antibody-antigen recognition","volume":"255","author":"Rini","year":"1992","journal-title":"Science"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5088\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:28:15Z","timestamp":1760178495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/21\/5088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,2]]},"references-count":107,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["molecules25215088"],"URL":"https:\/\/doi.org\/10.3390\/molecules25215088","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-37055\/v1","asserted-by":"object"}]},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,2]]}}}