{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:29:04Z","timestamp":1768462144384,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T00:00:00Z","timestamp":1709337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fauci Fellowships, National Italian American Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Coronaviruses are highly transmissible and pathogenic viruses for humans and animals. The vast quantity of information collected about SARS-CoV-2 during the pandemic helped to unveil details of the mechanisms behind the infection, which are still largely elusive. Recent research demonstrated that different class I\/II human leukocyte antigen (HLA) alleles might define an individual susceptibility to SARS-CoV-2 spreading, contributing to the differences in the distribution of the infection through different populations; additional studies suggested that the homolog of the HLA in cats, the feline leukocyte antigen (FLA), plays a pivotal role in the transmission of viruses. With these premises, this study aimed to exploit a bioinformatic approach for the prediction of the transmissibility potential of two distinct feline coronaviruses (FCoVs) in domestic cats (feline enteric coronavirus (FeCV) and feline infectious peritonitis virus (FIPV)) using SARS-CoV-2 as the reference model. We performed an epitope mapping of nonapeptides deriving from SARS-CoV-2, FeCV, and FIPV glycoproteins and predicted their affinities for different alleles included in the three main loci in class I FLAs (E, H, and K). The predicted complexes with the most promising affinities were then subjected to molecular docking and molecular dynamics simulations to provide insights into the stability and binding energies in the cleft. Results showed the FLA proteins encoded by alleles in the FLA-I H (H*00501 and H*00401) and E (E*01001 and E*00701) loci are largely responsive to several epitopes deriving from replicase and spike proteins of the analyzed coronaviruses. The analysis of the most affine epitope sequences resulting from the prediction can stimulate the development of anti-FCoV immunomodulatory strategies based on peptide drugs.<\/jats:p>","DOI":"10.3390\/life14030334","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T05:31:12Z","timestamp":1709530272000},"page":"334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Exploratory Bioinformatic Investigation of Cats\u2019 Susceptibility to Coronavirus-Deriving Epitopes"],"prefix":"10.3390","volume":"14","author":[{"given":"Michela","family":"Buonocore","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino, 1, 80137 Napoli, Italy"},{"name":"Department of Chemical Sciences, Research Centre on Bioactive Peptides (CIRPeB), University of Naples Federico II, Complesso Universitario di Monte Sant\u2032Angelo, Via Cintia, 80126 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-9807","authenticated-orcid":false,"given":"Davide","family":"De Biase","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orlando","family":"Paciello","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Via Federico Delpino, 1, 80137 Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"D\u2019Ursi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1177\/0300985814522077","article-title":"Feline infectious peritonitis: Still an enigma?","volume":"51","author":"Kipar","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1111\/jvim.16803","article-title":"Outcomes of treatment of cats with feline infectious peritonitis using parenterally administered remdesivir, with or without transition to orally administered GS-441524","volume":"37","author":"Coggins","year":"2023","journal-title":"J. Veter Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sweet, A., Andre, N., and Whittaker, G. (2022). RNA in-situ hybridization for pathology-based diagnosis of feline infectious peritonitis (FIP): Current diagnostics for FIP and comparison to the current gold standard. Qeios.","DOI":"10.32388\/NUN8KB"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1128\/jvi.66.2.956-965.1992","article-title":"Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages","volume":"66","author":"Olsen","year":"1992","journal-title":"J. Virol."},{"key":"ref_5","first-page":"7","article-title":"An overview of feline enteric coronavirus and infectious peritonitis virus infections","volume":"23","author":"Pedersen","year":"1995","journal-title":"Feline Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/978-1-4615-9373-7_38","article-title":"Role of circulating antibodies and thymus-dependent lymphocytes in production of effusive type feline infectious peritonitis after oral infection","volume":"45","author":"Hayashi","year":"1984","journal-title":"Mol. Biol. Pathog. Coronaviruses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1126\/science.abb7015","article-title":"Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2","volume":"368","author":"Shi","year":"2020","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41586-020-2334-5","article-title":"Infection of dogs with SARS-CoV-2","volume":"586","author":"Sit","year":"2020","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e05430","DOI":"10.1016\/j.heliyon.2020.e05430","article-title":"New putative animal reservoirs of SARS-CoV-2 in Italian fauna: A bioinformatic approach","volume":"6","author":"Buonocore","year":"2020","journal-title":"Heliyon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1600-065X.1999.tb01387.x","article-title":"Comparative genome organization of the major histocompatibility complex: Lessons from the Felidae","volume":"167","author":"Yuhki","year":"1999","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S1359-6446(03)03021-6","article-title":"Revival of the regulatory T cell: New targets for drug development","volume":"9","author":"Sutmuller","year":"2004","journal-title":"Drug Discov. Today"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4103\/bc.bc_16_21","article-title":"Major histocompatibility complex Class II-based therapy for stroke","volume":"7","author":"Borlongan","year":"2021","journal-title":"Brain Circ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s12975-019-00756-1","article-title":"A Novel Partial MHC Class II Construct, DRmQ, Inhibits Central and Peripheral Inflammatory Responses to Promote Neuroprotection in Experimental Stroke","volume":"11","author":"Lee","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/cns.13369","article-title":"Spleen participation in partial MHC class II construct neuroprotection in stroke","volume":"26","author":"Brown","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neuint.2016.10.007","article-title":"Partial MHC class II constructs as novel immunomodulatory therapy for stroke","volume":"107","author":"Benedek","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11011-013-9440-0","article-title":"A novel HLA-DR\u03b11-MOG-35-55 construct treats experimental stroke","volume":"29","author":"Benedek","year":"2014","journal-title":"Metab. Brain Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Correale, P., Mutti, L., Pentimalli, F., Baglio, G., Saladino, R.E., Sileri, P., and Giordano, A. (2020). HLA-B*44 and C*01 Prevalence Correlates with COVID-19 Spreading across Italy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155205"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liang, R., Sun, Y., Liu, Y., Wang, J., Wu, Y., Li, Z., Ma, L., Zhang, N., Zhang, L., and Wei, X. (2018). Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides. J. Virol., 92.","DOI":"10.1128\/JVI.01631-17"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s00251-004-0742-6","article-title":"The feline major histocompatibility complex is rearranged by an inversion with a breakpoint in the distal class I region","volume":"56","author":"Beck","year":"2005","journal-title":"Immunogenetics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1093\/jhered\/esm056","article-title":"Comparative Genomic Structure of Human, Dog, and Cat MHC: HLA, DLA, and FLA","volume":"98","author":"Yuhki","year":"2007","journal-title":"J. Hered."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s00251-013-0711-z","article-title":"Polymorphisms and tissue expression of the feline leukocyte antigen class I loci FLAI-E, FLAI-H, and FLAI-K","volume":"65","author":"Holmes","year":"2013","journal-title":"Immunogenetics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.vaccine.2016.01.017","article-title":"An initial examination of the potential role of T-cell immunity in protection against feline immunodeficiency virus (FIV) infection","volume":"34","author":"Aranyos","year":"2016","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.vaccine.2004.05.032","article-title":"Cellular immune responses to feline immunodeficiency virus (FIV) induced by dual-subtype FIV vaccine","volume":"23","author":"Omori","year":"2004","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1006\/cimm.1999.1574","article-title":"MHC-restricted protection of cats against FIV infection by adoptive transfer of immune cells from FIV-vaccinated donors","volume":"198","author":"Pu","year":"1999","journal-title":"Cell Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"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","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"UniProt","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0952-7915(95)80033-6","article-title":"Chemistry of peptides associated with MHC class I and class II molecules","volume":"7","author":"Rammensee","year":"1995","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","unstructured":"Schr\u00f6dinger, LLC (Maestro, 2023). Maestro, version 2023-2."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W443","DOI":"10.1093\/nar\/gky357","article-title":"Hpepdock: A web server for blind peptide\u2013protein docking based on a hierarchical algorithm","volume":"46","author":"Zhou","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1093\/bioinformatics\/btz459","article-title":"AutoDock CrankPep: Combining folding and docking to predict protein\u2013peptide complexes","volume":"35","author":"Zhang","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data","volume":"34","author":"Huang","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_36","first-page":"107","article-title":"ScanProsite: A reference implementation of a PROSITE scanning tool","volume":"1","author":"Gattiker","year":"2002","journal-title":"Appl. Bioinform."},{"key":"ref_37","unstructured":"NCBI Virus (2024, February 22). Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004\u201422 February 2024, Available online: www.ncbi.nlm.nih.gov\/labs\/virus\/vssi\/#\/."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1038\/s41467-019-10280-3","article-title":"Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors","volume":"10","author":"Kirchdoerfer","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/s41586-022-04466-x","article-title":"Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants","volume":"603","author":"Wang","year":"2022","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114857","DOI":"10.1016\/j.ejmech.2022.114857","article-title":"Rational design of the zonulin inhibitor AT1001 derivatives as potential anti SARS-CoV-2","volume":"244","author":"Rahimova","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1016\/j.cell.2021.05.046","article-title":"Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs","volume":"184","author":"Klaeger","year":"2021","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2022.01.015","article-title":"SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron","volume":"185","author":"Tarke","year":"2022","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/all.15066","article-title":"Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes","volume":"77","author":"Gattinger","year":"2022","journal-title":"Allergy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1038\/s41467-021-21767-3","article-title":"Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1128\/iai.37.3.1148-1155.1982","article-title":"Antigenic relationships among homologous structural polypeptides of porcine, feline, and canine coronaviruses","volume":"37","author":"Horzinek","year":"1982","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"D339","DOI":"10.1093\/nar\/gky1006","article-title":"The Immune Epitope Database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1265044","DOI":"10.3389\/fimmu.2023.1265044","article-title":"Experimental validation of immunogenic SARS-CoV-2 T cell epitopes identified by artificial intelligence","volume":"14","author":"Federico","year":"2023","journal-title":"Front Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"110214","DOI":"10.1016\/j.celrep.2021.110214","article-title":"Recruitment of highly cytotoxic CD8(+) T cell receptors in mild SARS-CoV-2 infection","volume":"38","author":"Wagner","year":"2022","journal-title":"Cell Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41564-022-01106-y","article-title":"SARS-CoV-2-specific T-cell epitope repertoire in convalescent and mRNA-vaccinated individuals","volume":"7","author":"Luxenburger","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100204","DOI":"10.1016\/j.xcrm.2021.100204","article-title":"Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases","volume":"2","author":"Tarke","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41586-021-03653-6","article-title":"BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans","volume":"595","author":"Sahin","year":"2021","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-021-03841-4","article-title":"Rapid and stable mobilization of CD8(+) T cells by SARS-CoV-2 mRNA vaccine","volume":"597","author":"Oberhardt","year":"2021","journal-title":"Nature"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4401","DOI":"10.1016\/j.cell.2021.06.029","article-title":"Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses","volume":"184","author":"Nathan","year":"2021","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/j.vaccine.2010.12.106","article-title":"Screening and identification of T helper 1 and linear immunodominant antibody-binding epitopes in the spike 2 domain and the nucleocapsid protein of feline infectious peritonitis virus","volume":"29","author":"Satoh","year":"2011","journal-title":"Vaccine"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/334\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:08:14Z","timestamp":1760105294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,2]]},"references-count":54,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["life14030334"],"URL":"https:\/\/doi.org\/10.3390\/life14030334","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,2]]}}}