Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses
Identifieur interne : 001292 ( Pmc/Corpus ); précédent : 001291; suivant : 001293Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses
Auteurs : Bruno Tilocca ; Alessio Soggiu ; Maurizio Sanguinetti ; Vincenzo Musella ; Domenico Britti ; Luigi Bonizzi ; Andrea Urbani ; Paola RoncadaSource :
- Microbes and Infection [ 1286-4579 ] ; 2020.
Abstract
Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an
Url:
DOI: 10.1016/j.micinf.2020.04.002
PubMed: 32302675
PubMed Central: 7156246
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PMC:7156246Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses</title><author><name sortKey="Tilocca, Bruno" sort="Tilocca, Bruno" uniqKey="Tilocca B" first="Bruno" last="Tilocca">Bruno Tilocca</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Soggiu, Alessio" sort="Soggiu, Alessio" uniqKey="Soggiu A" first="Alessio" last="Soggiu">Alessio Soggiu</name><affiliation><nlm:aff id="aff2">Department of Biomedical, Surgical and Dental Sciences– One Health Unit, University of Milano, Via Celoria n10, 20133, Milano, Italy</nlm:aff></affiliation></author><author><name sortKey="Sanguinetti, Maurizio" sort="Sanguinetti, Maurizio" uniqKey="Sanguinetti M" first="Maurizio" last="Sanguinetti">Maurizio Sanguinetti</name><affiliation><nlm:aff id="aff3">Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo S. Vito 1, 00168, Roma, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Dipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli 8, 00168, Roma, Italy</nlm:aff></affiliation></author><author><name sortKey="Musella, Vincenzo" sort="Musella, Vincenzo" uniqKey="Musella V" first="Vincenzo" last="Musella">Vincenzo Musella</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Britti, Domenico" sort="Britti, Domenico" uniqKey="Britti D" first="Domenico" last="Britti">Domenico Britti</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Bonizzi, Luigi" sort="Bonizzi, Luigi" uniqKey="Bonizzi L" first="Luigi" last="Bonizzi">Luigi Bonizzi</name><affiliation><nlm:aff id="aff2">Department of Biomedical, Surgical and Dental Sciences– One Health Unit, University of Milano, Via Celoria n10, 20133, Milano, Italy</nlm:aff></affiliation></author><author><name sortKey="Urbani, Andrea" sort="Urbani, Andrea" uniqKey="Urbani A" first="Andrea" last="Urbani">Andrea Urbani</name><affiliation><nlm:aff id="aff3">Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo S. Vito 1, 00168, Roma, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Dipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli 8, 00168, Roma, Italy</nlm:aff></affiliation></author><author><name sortKey="Roncada, Paola" sort="Roncada, Paola" uniqKey="Roncada P" first="Paola" last="Roncada">Paola Roncada</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32302675</idno><idno type="pmc">7156246</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156246</idno><idno type="RBID">PMC:7156246</idno><idno type="doi">10.1016/j.micinf.2020.04.002</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001292</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001292</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses</title><author><name sortKey="Tilocca, Bruno" sort="Tilocca, Bruno" uniqKey="Tilocca B" first="Bruno" last="Tilocca">Bruno Tilocca</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Soggiu, Alessio" sort="Soggiu, Alessio" uniqKey="Soggiu A" first="Alessio" last="Soggiu">Alessio Soggiu</name><affiliation><nlm:aff id="aff2">Department of Biomedical, Surgical and Dental Sciences– One Health Unit, University of Milano, Via Celoria n10, 20133, Milano, Italy</nlm:aff></affiliation></author><author><name sortKey="Sanguinetti, Maurizio" sort="Sanguinetti, Maurizio" uniqKey="Sanguinetti M" first="Maurizio" last="Sanguinetti">Maurizio Sanguinetti</name><affiliation><nlm:aff id="aff3">Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo S. Vito 1, 00168, Roma, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Dipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli 8, 00168, Roma, Italy</nlm:aff></affiliation></author><author><name sortKey="Musella, Vincenzo" sort="Musella, Vincenzo" uniqKey="Musella V" first="Vincenzo" last="Musella">Vincenzo Musella</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Britti, Domenico" sort="Britti, Domenico" uniqKey="Britti D" first="Domenico" last="Britti">Domenico Britti</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author><author><name sortKey="Bonizzi, Luigi" sort="Bonizzi, Luigi" uniqKey="Bonizzi L" first="Luigi" last="Bonizzi">Luigi Bonizzi</name><affiliation><nlm:aff id="aff2">Department of Biomedical, Surgical and Dental Sciences– One Health Unit, University of Milano, Via Celoria n10, 20133, Milano, Italy</nlm:aff></affiliation></author><author><name sortKey="Urbani, Andrea" sort="Urbani, Andrea" uniqKey="Urbani A" first="Andrea" last="Urbani">Andrea Urbani</name><affiliation><nlm:aff id="aff3">Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo S. Vito 1, 00168, Roma, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Dipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli 8, 00168, Roma, Italy</nlm:aff></affiliation></author><author><name sortKey="Roncada, Paola" sort="Roncada, Paola" uniqKey="Roncada P" first="Paola" last="Roncada">Paola Roncada</name><affiliation><nlm:aff id="aff1">Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Microbes and Infection</title><idno type="ISSN">1286-4579</idno><idno type="eISSN">1769-714X</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an <italic>in-silico</italic> survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhou, X" uniqKey="Zhou X">X. Zhou</name></author><author><name sortKey="Wu, Z" uniqKey="Wu Z">Z. Wu</name></author><author><name sortKey="Yu, R" uniqKey="Yu R">R. Yu</name></author><author><name sortKey="Cao, S" uniqKey="Cao S">S. Cao</name></author><author><name sortKey="Fang, W" uniqKey="Fang W">W. Fang</name></author><author><name sortKey="Jiang, Z" uniqKey="Jiang Z">Z. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Microbes Infect</journal-id><journal-id journal-id-type="iso-abbrev">Microbes Infect</journal-id><journal-title-group><journal-title>Microbes and Infection</journal-title></journal-title-group><issn pub-type="ppub">1286-4579</issn><issn pub-type="epub">1769-714X</issn><publisher><publisher-name>Institut Pasteur. Published by Elsevier Masson SAS.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32302675</article-id><article-id pub-id-type="pmc">7156246</article-id><article-id pub-id-type="publisher-id">S1286-4579(20)30053-8</article-id><article-id pub-id-type="doi">10.1016/j.micinf.2020.04.002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Comparative computational analysis of SARS-CoV-2 nucleocapsid protein epitopes in taxonomically related coronaviruses</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Tilocca</surname><given-names>Bruno</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Soggiu</surname><given-names>Alessio</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Sanguinetti</surname><given-names>Maurizio</given-names></name><xref rid="aff3" ref-type="aff">c</xref><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Musella</surname><given-names>Vincenzo</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Britti</surname><given-names>Domenico</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Bonizzi</surname><given-names>Luigi</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Urbani</surname><given-names>Andrea</given-names></name><email>andrea.urbani@unicatt.it</email><xref rid="aff3" ref-type="aff">c</xref><xref rid="aff4" ref-type="aff">d</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib><contrib contrib-type="author" id="au8"><name><surname>Roncada</surname><given-names>Paola</given-names></name><email>roncada@unicz.it</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Health Science, University “Magna Græcia” of Catanzaro, Viale Europa, 88100, Catanzaro, Italy</aff><aff id="aff2"><label>b</label>Department of Biomedical, Surgical and Dental Sciences– One Health Unit, University of Milano, Via Celoria n10, 20133, Milano, Italy</aff><aff id="aff3"><label>c</label>Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, Largo S. Vito 1, 00168, Roma, Italy</aff><aff id="aff4"><label>d</label>Dipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario Agostino Gemelli, Largo A. Gemelli 8, 00168, Roma, Italy</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Prof. Paola Roncada, Viale Europa, 88100, Catanzaro, Italy. <email>roncada@unicz.it</email></corresp><corresp id="cor2"><label>∗∗</label>Co-Corresponding author. Prof. Andrea Urbani, Largo San Vito n.1, 00168, Roma, Italy. <email>andrea.urbani@unicatt.it</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>14</day><month>4</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>14</day><month>4</month><year>2020</year></pub-date><history><date date-type="received"><day>3</day><month>4</month><year>2020</year></date><date date-type="accepted"><day>7</day><month>4</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Institut Pasteur</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><p>Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an <italic>in-silico</italic> survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies.</p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>SARS-CoV-2</kwd><kwd>COVID-19</kwd><kwd>Coronavirus</kwd><kwd>Personalized medicine</kwd><kwd>Diagnosis</kwd></kwd-group></article-meta></front><body><p id="p0010">As of 30 March 2020, SARS-CoV-2 diffusion becomes a world-wide issue with nearly all countries of the globe being interested in a steadily growing number of infected subjects and the tendentially increasing mortality rate, by means of the COVID-19, in the newly involved countries. On the other hand, the SARS-CoV-2 diffusion seems to be approaching an end in Wuhan, China, its original epicentre. Here, the registration of new COVID-19 cases is currently near zero, enabling the development of fair and unbiased statistics on the COVID-19 data in the Hubei region [<xref rid="bib1" ref-type="bibr">1</xref>,<xref rid="bib2" ref-type="bibr">2</xref>]. The thorough review of the patient cases describes, besides the common pulmonary issues, a wide variety of sequelae reported by diverse patients from diverse hospitals following the viral infection. These range from hearth injury until hepatic and kidney failure, hindering a clear depiction of the pathogenetic mechanisms of the novel virus and the definition of informative clinical signs pathognomonic of SARS-CoV-2 infection [<xref rid="bib3" ref-type="bibr">3</xref>,<xref rid="bib4" ref-type="bibr">4</xref>]. Although the appropriate consideration of the patient’s health status is of crucial importance while assessing COVID-19 impact, it is believed that the severity of COVID-19 depends on a plurality of factors that include, among others, the load of viral particles transmitted between individuals, the transmission route and the individual immune system efficiency [<xref rid="bib5" ref-type="bibr">5</xref>,<xref rid="bib6" ref-type="bibr">6</xref>].</p><p id="p0015">The causal agent of the current pandemic has been timely classified as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [<xref rid="bib7" ref-type="bibr">7</xref>]. In humans, coronavirus infections are commonly manifested through weak clinical signs attributable to the seasonal flu-like symptoms. Nevertheless, the last two decades have already seen a couple of severe manifestations of the coronavirus infection. The first outbreak was described as the SARS epidemy registered in 2003 in China [<xref rid="bib8" ref-type="bibr">8</xref>]; whereas a second coronavirus outbreak, known as Middle East Respiratory Syndrome (MERS), dates back to 2012 in Saudi Arabia. Besides humans [<xref rid="bib9" ref-type="bibr">9</xref>], SARS viruses are able to infecting a wide plethora of animals such as birds and mammals, including synanthropic birds, dogs, camels, dromedaries, and pangolins [<xref rid="bib10" ref-type="bibr">10</xref>]. SARS-CoV-2 is a member of the genus Betacoronavirus, featured by a positive-sense, single-stranded RNA genome of approximately 30 Kbs. The viral genome encodes for a relatively low number of proteins classified as either structural or nonstructural ones. Among structural proteins, the spike glycoprotein (S), envelope protein (E), membrane protein (M) and the nucleocapsid protein (NC) are the major ones [<xref rid="bib7" ref-type="bibr">7</xref>].</p><p id="p0020">Nucleocapsid protein is a 50 KDa protein commonly involved in the replication, transcription and packaging of the viral genome, other than hindering the reproductive cycle of the host cell [<xref rid="bib11" ref-type="bibr">11</xref>]. Also, NC is the most abundant protein in coronaviruses, is highly immunogenic and its amino acid sequence is normally conserved, making of this protein a suitable candidate target for both vaccine formulations and diagnostic assays [<xref rid="bib12" ref-type="bibr">12</xref>,<xref rid="bib13" ref-type="bibr">13</xref>]. Previous studies on SARS-CoV reported NC protein epitopes as capable of eliciting a massive production of antibodies in infected subjects while its prevalence was significantly reduced in convalescent patients, suggesting such epitopes as candidates for the design of diagnostic tools. Contrarywise, epitopes triggering T-cell response might confer prolonged protection, in some cases estimated up to 11 years; thus, representing a valid alternative for the design of prophylactic measures [<xref rid="bib14" ref-type="bibr">14</xref>].</p><p id="p0025">Acknowledged the recent identification of SARS-CoV-2, several research lines are currently ongoing to address the multitude of facets of this pandemic issue. Among these, defining the immunological features of the SARS-CoV-2 might provide crucial knowledge for the design of efficient diagnostic tools and/or vaccine strategy. In addition, comparing epitopes of taxonomically related viruses can help to track an eventual cross-protection occurring between humans and the domestic animals, meant as the consequence of the continuous interrelation that, for various reasons, occur among the diverse animal species.</p><p id="p0030">In the present study, we provide an <italic>in-silico</italic> survey of the major NC epitopes and compare them with the NC immunological domains of taxonomically related coronaviruses with tropism for synanthropic animal species that are closely inter-related with the human beings population all over the world. Given the ongoing status of the pandemic, both epitopes eliciting antibodies production and T-cell responses will be taken into account, as even the short-term antibody production can be protective for both human and animals; thus, help to weaken the clinical manifestation of the SARS-CoV-2 infection.</p><sec id="sec1"><label>2</label><title>Material and methods</title><sec id="sec1.1"><label>2.1</label><title>Data collection</title><p id="p0035">The virus species and accession number of the proteins employed in this survey are provided in <xref rid="tbl1" ref-type="table">Table 1</xref>. Nucleocapsid protein sequences were downloaded from the NCBI Protein repository (<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/protein/" id="intref0010">https://www.ncbi.nlm.nih.gov/protein/</ext-link>) except for the Pangolin nucleocapsid protein. The latter was obtained from the recent publication of Zhang et al. (supplementary material: [<xref rid="bib13" ref-type="bibr">13</xref>], <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.cub.2020.03.022" id="intref0015">https://doi.org/10.1016/j.cub.2020.03.022</ext-link>) as no protein sequence for the pangolin coronavirus was available at the time of the study.<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Selected virus overview. The table lists the viral specimens employed in this study along with the relative details.</p></caption><alt-text id="alttext0030">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Virus</th><th>NCBI TaxID</th><th>NCBI Genome</th><th>Protein GI</th></tr></thead><tbody><tr><td>Bat CoV RaTG13</td><td>693998</td><td>MN996532</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:QHR63308.1" id="intref0035a">QHR63308.1</ext-link></td></tr><tr><td>SARS-CoV</td><td>694009</td><td>NC_004718.3</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:AAX16200.1" id="intref0030">AAX16200.1</ext-link></td></tr><tr><td>Pangolin CoV</td><td>2708335</td><td>MT084071</td><td>NC_PangolinCoV from [<xref rid="bib13" ref-type="bibr">13</xref>]</td></tr><tr><td>Camel CoV</td><td>1335626</td><td>MK967708</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:QGV13487.1" id="intref0035b">QGV13487.1</ext-link></td></tr><tr><td>MERS-CoV</td><td>1335626</td><td>NC_019843.3</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:YP_009047211.1" id="intref0035">YP_009047211.1</ext-link></td></tr><tr><td>Dromedarius CoV</td><td>1335626</td><td>MH259486</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:QCI31487.1" id="intref0035c">QCI31487.1</ext-link></td></tr><tr><td>H-Enteric CoV</td><td>166124</td><td>FJ415324</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:ACJ35489.1" id="intref0040">ACJ35489.1</ext-link></td></tr><tr><td>Canine CoV</td><td>215681</td><td>KX432213</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:AQT26504.1" id="intref0045">AQT26504.1</ext-link></td></tr><tr><td>Bovine CoV</td><td>11128</td><td>NC_003045</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:NP_150083.1" id="intref0050">NP_150083.1</ext-link></td></tr><tr><td>Avian CoV</td><td>11120</td><td>NC_001451</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:NP_040838.1" id="intref0055">NP_040838.1</ext-link></td></tr></tbody></table></table-wrap></p></sec><sec id="sec1.2"><label>2.2</label><title>Computational processing of the protein sequences</title><p id="p0040">The selected protein sequences were analyzed by using the Basic Local Alignment Search Tool for protein sequences (pBLAST) [<xref rid="bib15" ref-type="bibr">15</xref>]. This tool implements the BLOSUM62 algorithm to compare protein sequences and calculates the statistical significance of matches as means of e-values. Multiple sequence alignment was performed by keeping default settings. Only the best hit for each coronavirus was considered and hits with alignment length less than or equal to 4 amino acids were manually removed. Statistically significant matches were employed for calculating the similarity tree of the taxonomically-related coronaviruses on the basis of their relative NC protein sequences. Fast minimum evolution algorithm was employed to produce a tree from given distances between sequences by setting a maximum fraction of mismatch between pairs of sequences of 0.85.</p></sec><sec id="sec1.3"><label>2.3</label><title>Structural mapping of epitopes to PDB structures</title><p id="p0045">The mapped protein epitopes to SARS-CoV-2 NC protein (YP_009724397.2 |P0DTC9) were also mapped on two available PDB structures using the PyMOL Molecular Graphics System, Version 2.3.4 (Schrödinger, LLC.). Briefly, two NC 3D structure available in the RCSB PDB database (6M3M and 2JW8, <ext-link ext-link-type="uri" xlink:href="https://www.rcsb.org/" id="intref0020">https://www.rcsb.org/</ext-link>) covering respectively residues number 47–173 and 247–364 were downloaded and mapping epitopes were visualized through PyMOL. Distances between residues representing different sequences located on the surface of the 3D model were measured using the wizard measurement to identify possible areas of cross-reactivity and antigen-binding.</p></sec></sec><sec id="sec2"><label>3</label><title>Results</title><p id="p0050">The whole aminoacidic sequences of the nucleocapsid protein from the selected coronavirus representatives were compared to assess the similarity level existing between the conserved protein sequences of the taxonomically related viruses. <xref rid="fig1" ref-type="fig">Fig. 1</xref>depicts the phylogenetic classification of the coronaviruses on the basis of their NC protein. In this view, bat coronavirus RaTG13 is classified as the most similar to the circulating SARS-CoV-2, followed by SARS-CoV and the pangolin NC protein sequence. A separate clade is reserved to MERS-CoV and the NC protein sequences of the coronaviruses with tropism for camels (<italic>Camelus bactrianus</italic>) and dromedaries (<italic>Camelus dromedarius</italic>). Nucleocapsid proteins of bovine, canine and human enteric coronaviruses are depicted as sister groups of a third clade with lower similarity in relation to SARS-CoV-2; whereas, the avian coronavirus cluster apart since featured by the lowest similarity with the circulating SARS-CoV-2. Phylogenetic classification of the viruses on the basis of the NC protein sequence is further supported by the multiple sequence alignment performed on the whole protein sequence. Here, NC from bat coronavirus RaTG13 shows a similarity with the SARS-CoV-2 homologue slightly above 99%. NC from SARS-CoV, instead, is approximately 90.3% similar with the causal agent of COVID-19, followed by the NC sequence from pangolin CoV with almost 88% sequence similarity. Other selected coronavirus representatives have minor sequence similarity as reported in <xref rid="tbl2" ref-type="table">Table 2</xref>.<fig id="fig1"><label>Fig. 1</label><caption><p>Phylogenetic classification of the selected coronaviruses according to the whole nucleocapsid protein sequence homology.</p></caption><alt-text id="alttext0015">Fig. 1</alt-text><graphic xlink:href="gr1_lrg"></graphic></fig><table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Multiple sequence alignment of the Nucleocapside protein from taxonomically-related coronaviruses.</p></caption><alt-text id="alttext0035">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Virus</th><th>Protein GI</th><th>Identity (%)</th><th>Alignment length</th><th>Mismatches</th><th>e-value</th></tr></thead><tbody><tr><td>Bat CoV</td><td>QHR63308.1</td><td>99.045</td><td>419</td><td>4</td><td>–</td></tr><tr><td>SARS-CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:AAX16200.1" id="intref0060">AAX16200.1</ext-link></td><td>90.284</td><td>422</td><td>38</td><td>–</td></tr><tr><td>Pangolin CoV</td><td>NC_PangolinCoV</td><td>87.857</td><td>420</td><td>8</td><td>–</td></tr><tr><td>Camel CoV</td><td>QGV13487.1</td><td>48.492</td><td>398</td><td>179</td><td>7.14e-93</td></tr><tr><td>MERS-CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:YP_009047211.1" id="intref0065">YP_009047211.1</ext-link></td><td>48.492</td><td>398</td><td>179</td><td>7.14e-93</td></tr><tr><td>Dromedarius CoV</td><td>QCI31487.1</td><td>48.492</td><td>398</td><td>179</td><td>9.55e-93</td></tr><tr><td>Bovine CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:NP_150083.1" id="intref0070">NP_150083.1</ext-link></td><td>38.938</td><td>339</td><td>158</td><td>5.97e-54</td></tr><tr><td>H-Enteric CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:ACJ35489.1" id="intref0075">ACJ35489.1</ext-link></td><td>38.348</td><td>339</td><td>160</td><td>1.98e-54</td></tr><tr><td>Canine CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:AQT26504.1" id="intref0080">AQT26504.1</ext-link></td><td>38.348</td><td>339</td><td>160</td><td>9.97e-54</td></tr><tr><td>Avian CoV</td><td><ext-link ext-link-type="uri" xlink:href="ncbi-p:NP_040838.1" id="intref0085">NP_040838.1</ext-link></td><td>29.664</td><td>327</td><td>210</td><td>2.00e-31</td></tr></tbody></table></table-wrap></p><p id="p0055">Nucleocapsid protein sequences were further investigated for the presence of major immunogenic sequences capable of eliciting either antibodies production or eliciting T-cell response (<xref rid="tbl3" ref-type="table">Table 3</xref>) according to the evidence reported in Ref. [<xref rid="bib14" ref-type="bibr">14</xref>].<table-wrap position="float" id="tbl3"><label>Table 3</label><caption><p>Selected nucleocapsid protein epitopes.</p></caption><alt-text id="alttext0040">Table 3</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Epitope</th><th>Virus</th><th>% Identity</th><th>Length</th><th>Alignment length</th><th>Position</th><th>e-value</th></tr></thead><tbody><tr><td rowspan="9">KHWPQIAQ<break></break>FAPSASAFF</td><td>SARS-CoV</td><td>100</td><td>17</td><td>17</td><td>300–316</td><td>2.46e-16</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>17</td><td>299–315</td><td>2.46e-16</td></tr><tr><td>Dromedarius CoV</td><td>78.571</td><td></td><td>14</td><td>293–306</td><td>7.55e-09</td></tr><tr><td>Camel CoV</td><td>78.571</td><td></td><td>14</td><td>293–306</td><td>7.55e-09</td></tr><tr><td>MERS-CoV</td><td>78.571</td><td></td><td>14</td><td>293–306</td><td>7.55e-09</td></tr><tr><td>H-Enteric CoV</td><td>52.941</td><td></td><td>17</td><td>308–324</td><td>7.05e-04</td></tr><tr><td>Canine CoV</td><td>52.941</td><td></td><td>17</td><td>308–324</td><td>7.05e-04</td></tr><tr><td>Bovine CoV</td><td>52.941</td><td></td><td>17</td><td>308–324</td><td>8.30e-05</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>16</td><td>290–305</td><td>2.72e-16</td></tr><tr><td rowspan="10">AQFAPSA<break></break>SAFFGMSR</td><td>SARS-CoV</td><td>100</td><td>15</td><td>15</td><td>306–320</td><td>3.34e-13</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>15</td><td>305–319</td><td>3.34e-13</td></tr><tr><td>Dromedarius CoV</td><td>71.429</td><td></td><td>14</td><td>297–310</td><td>2.75e-06</td></tr><tr><td>Camel CoV</td><td>71.429</td><td></td><td>14</td><td>297–310</td><td>2.75e-06</td></tr><tr><td>MERS-CoV</td><td>71.429</td><td></td><td>14</td><td>297–310</td><td>2.75e-06</td></tr><tr><td>H-Enteric CoV</td><td>63.636</td><td></td><td>11</td><td>314–324</td><td>0.001</td></tr><tr><td>Canine CoV</td><td>63.636</td><td></td><td>11</td><td>314–324</td><td>0.001</td></tr><tr><td>Avian CoV</td><td>58.333</td><td></td><td>12</td><td>276–286</td><td>13</td></tr><tr><td>Bovine CoV</td><td>63.636</td><td></td><td>11</td><td>314–324</td><td>1.73e-04</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>15</td><td>295–309</td><td>3.33e-14</td></tr><tr><td rowspan="10">PKGFYAEG<break></break>SRGGSQASSR</td><td>SARS-CoV</td><td>100</td><td>18</td><td>18</td><td>169–186</td><td>2.32e-15</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>18</td><td>168–185</td><td>2.32e-15</td></tr><tr><td>Dromedarius CoV</td><td>61.111</td><td></td><td>18</td><td>157–174</td><td>1.02e-04</td></tr><tr><td>Camel CoV</td><td>61.111</td><td></td><td>18</td><td>157–174</td><td>1.02e-04</td></tr><tr><td>MERS-CoV</td><td>61.111</td><td></td><td>18</td><td>157–174</td><td>1.02e-04</td></tr><tr><td>H-Enteric CoV</td><td>48</td><td></td><td>25</td><td>183–207</td><td>2.88e-04</td></tr><tr><td>Canine CoV</td><td>48</td><td></td><td>25</td><td>183–207</td><td>2.88e-04</td></tr><tr><td>Avian CoV</td><td>100</td><td></td><td>5</td><td>183–187</td><td>0.15</td></tr><tr><td>Bovine CoV</td><td>48</td><td></td><td>25</td><td>183–207</td><td>3.40e-05</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>18</td><td>168–185</td><td>2.30e-16</td></tr><tr><td rowspan="10">QFAPSASAF<break></break>FGMSRIGM</td><td>SARS-CoV</td><td>100</td><td>17</td><td>17</td><td>307–323</td><td>6.91e-16</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>17</td><td>306–322</td><td>6.91e-16</td></tr><tr><td>Dromedarius CoV</td><td>81.818</td><td></td><td>11</td><td>300–310</td><td>1.54e-05</td></tr><tr><td>Camel CoV</td><td>81.818</td><td></td><td>11</td><td>300–310</td><td>1.54e-05</td></tr><tr><td>MERS-CoV</td><td>81.818</td><td></td><td>11</td><td>300–310</td><td>1.54e-05</td></tr><tr><td>H-Enteric CoV</td><td>50</td><td></td><td>16</td><td>309–324</td><td>0.004</td></tr><tr><td>Canine CoV</td><td>50</td><td></td><td>16</td><td>309–324</td><td>0.004</td></tr><tr><td>Avian CoV</td><td>53.846</td><td></td><td>13</td><td>276–287</td><td>7.8</td></tr><tr><td>Bovine CoV</td><td>50</td><td></td><td>16</td><td>309–324</td><td>4.73e-04</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>17</td><td>296–312</td><td>6.88e-17</td></tr><tr><td rowspan="10">QLPQGTTLPKGF<break></break>YAEGSRGGSQ</td><td>SARS-CoV</td><td>100</td><td>22</td><td>22</td><td>161–182</td><td>7.79e-20</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>22</td><td>160–181</td><td>7.79e-20</td></tr><tr><td>H-Enteric CoV</td><td>66.667</td><td></td><td>15</td><td>177–191</td><td>3.16e-05</td></tr><tr><td>Canine CoV</td><td>66.667</td><td></td><td>15</td><td>177–191</td><td>3.16e-05</td></tr><tr><td>Dromedarius CoV</td><td>61.111</td><td></td><td>18</td><td>153–170</td><td>4.88e-04</td></tr><tr><td>Camel CoV</td><td>61.111</td><td></td><td>18</td><td>153–170</td><td>4.88e-04</td></tr><tr><td>MERS-CoV</td><td>61.111</td><td></td><td>18</td><td>153–170</td><td>4.88e-04</td></tr><tr><td>Avian CoV</td><td>100</td><td></td><td>5</td><td>183–187</td><td>0.22</td></tr><tr><td>Bovine CoV</td><td>66.667</td><td></td><td>15</td><td>177–191</td><td>3.72e-06</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>22</td><td>160–181</td><td>7.75e-21</td></tr><tr><td rowspan="9">YNVTQAFGR<break></break>RGPEQTQGNF</td><td>SARS-CoV</td><td>100</td><td>19</td><td>19</td><td>269–287</td><td>4.02e-18</td></tr><tr><td>Bat CoV</td><td>100</td><td></td><td>19</td><td>268–286</td><td>4.02e-18</td></tr><tr><td>Dromedarius CoV</td><td>63.158</td><td></td><td>19</td><td>260–278</td><td>1.86e-06</td></tr><tr><td>Camel CoV</td><td>63.158</td><td></td><td>19</td><td>260–278</td><td>1.86e-06</td></tr><tr><td>MERS-CoV</td><td>63.158</td><td></td><td>19</td><td>260–278</td><td>1.86e-06</td></tr><tr><td>H-Enteric CoV</td><td>58.824</td><td></td><td>17</td><td>282–295</td><td>3.32e-04</td></tr><tr><td>Canine CoV</td><td>58.824</td><td></td><td>17</td><td>282–295</td><td>3.32e-04</td></tr><tr><td>Bovine CoV</td><td>58.824</td><td></td><td>17</td><td>282–295</td><td>3.91e-05</td></tr><tr><td>Pangolin CoV</td><td>100</td><td></td><td>15</td><td>261–275</td><td>2.40e-14</td></tr></tbody></table></table-wrap></p><p id="p0060">Epitopes falling within protein sequence domains for which homology modelling based on the experimental crystallographic structure is available are mapped and provided in <xref rid="fig2" ref-type="fig">Fig. 2</xref>and <xref rid="fig3" ref-type="fig">Fig. 3</xref>; whereas, the full list of the tested epitopes against the selected viral nucleocapsid protein sequences is provided as Supplementary material (S1).<fig id="fig2"><label>Fig. 2</label><caption><p>Epitope mapping into 6M3M structural model. The figure depicts mapping of the epitope sequence AQFAPSASAFFGMSR (yellow) and QFAPSASAFFGMSRIGM (cyan). A-panel shows the surface mapping of the epitopes in the D structure of the nucleocapsid protein domain. B-panel highlights distances occurring between the mapped epitopes.</p></caption><alt-text id="alttext0020">Fig. 2</alt-text><graphic xlink:href="gr2_lrg"></graphic></fig><fig id="fig3"><label>Fig. 3</label><caption><p>Epitope mapping into 2JW8 structural model. The figure depicts mapping of the epitope sequence PKGFYAEGSRGGSQASSR (blue), YNVTQAFGRRGPEQTQGNF (orange), AQFAPSASAFFGMSR (green) and KHWPQIAQFAPSASAFF (red). A-panel shows the surface mapping of the epitopes in the D structure of the nucleocapsid protein domain. B- panel highlights distances occurring between mapped epitopes.</p></caption><alt-text id="alttext0025">Fig. 3</alt-text><graphic xlink:href="gr3_lrg"></graphic></fig></p><p id="p0065">Some of the mapped epitopes are “conserved” between the circulating SARS-CoV-2, the SARS-CoV, bat RaTG13 CoV and the pangolin CoV NC protein, <italic>i.e.</italic> the clade including the most similar specimens; whereas, other epitopes are “shared” with a multitude of coronavirus, including those from other animals that clustered as dissimilar from the circulating SARS-CoV-2 (<xref rid="fig1" ref-type="fig">Fig. 1</xref>, <xref rid="tbl3" ref-type="table">Table 3</xref> and <xref rid="appsec1" ref-type="sec">Table S1</xref>). With regard to interspecies distribution, all epitopes are identified in the bat RaTG13 CoV and SARS-CoV, whilst the pangolin NC sequence fail to significatively align two of the epitope sequences classified as B-cells activating. In addition, epitopes sequence comparison highlights that both bat RaTG13 coronavirus and SARS-CoV scored 100% sequence identity with SARS-CoV-2 epitopes, whereas NC protein from pangolin results in a handful of epitopes sharing a lower percentage of identity with the novel 2019 virus (<xref rid="tbl3" ref-type="table">Table 3</xref> and <xref rid="appsec1" ref-type="sec">Table S1</xref>).</p><p id="p0070">Besides the most similar virus specimens, some epitope sequences are also identified in the viruses responsible for previous coronavirus outbreaks and coronaviruses with tropism for synanthropic and domestic animals. Although identity percentage with SARS-CoV-2 is below 100%, high homology levels have been scored for MERS-CoV, camel-CoV, dromedary-CoV. Interestingly, bovine CoV, canine CoV, human enteric CoV and avian-CoV have also shared epitope sequences, despite the dissimilarity highlighted on the basis of the whole NC sequence (<xref rid="fig1" ref-type="fig">Fig. 1</xref>, <xref rid="tbl3" ref-type="table">Table 3</xref>).</p><p id="p0075">Structural mapping of the epitopes listed in <xref rid="tbl3" ref-type="table">Table 3</xref> into two high-fidelity 3D models of the NC protein domains (6M3M and 2JW8 entries of PDB database) shows that a plurality of epitopes is mapped adjacent each other in a well define structural domain which is defined by a radius of approximately 15 Å (<xref rid="fig2" ref-type="fig">Fig. 2</xref>, <xref rid="fig3" ref-type="fig">Fig. 3</xref>). Interestingly, these epitopes are coded in distal primary sequence region of the NC protein which forms a conformational immunogenic domain (<xref rid="fig2" ref-type="fig">Fig. 2</xref>, <xref rid="fig3" ref-type="fig">Fig. 3</xref>). Unfortunately, not all the investigated epitopes can be mapped in the tridimensional model of the NC protein due to the lack of confident model structure for the whole protein length.</p></sec><sec id="sec3"><label>4</label><title>Discussion</title><p id="p0080">The current health emergency raised by the COVID-19 aroused the interest of the world-wide scientific community that actively operates under diverse research lines on the attempt to address the multiple facets of this pandemic issue, including the elucidation of the immunological peculiarities of the novel virus.</p><p id="p0085">The present study provides an <italic>in-silico</italic> survey of the major epitope sequences of the nucleocapsid protein from taxonomically related coronaviruses. Coronavirus infections and outbreaks were already registered in the past decades in both humans and animals [<xref rid="bib8" ref-type="bibr">8</xref>,<xref rid="bib9" ref-type="bibr">9</xref>]. Thus, investigating whether immunological features of taxonomically related viruses are shared with the SARS-CoV-2 might be helpful for planning innovative diagnostic and prophylactic interventions. According to the One-Health approach, defining the distribution of epitopes among viruses capable of infecting synanthropic and/or domestic animals might represent a key strategy for assessing the plausible occurrence of cross-protection elicited by the continuous inter-relation existing between human and animal population. In this view, exposure to epitopes from synanthropic animals might confer partial protection from SARS-CoV-2 infection. This would explain, at least in part, the early detection of class G immunoglobulins in newly infected subjects and the big divergence occurring in the clinical manifestation of the SARS-CoV-2 infections, other than preventing epitopes-exposed subjects from the severe form of COVID-19 [<xref rid="bib16" ref-type="bibr">16</xref>].</p><p id="p0090">Nucleocapsid protein is a highly conserved protein involved in the active phase of the viral infection. Being highly immunogenic is commonly targeted in studies aimed at developing alternative diagnostic tools and prophylactic strategies [<xref rid="bib11" ref-type="bibr">11</xref>,<xref rid="bib14" ref-type="bibr">14</xref>,<xref rid="bib17" ref-type="bibr">[17]</xref>, <xref rid="bib18" ref-type="bibr">[18]</xref>, <xref rid="bib19" ref-type="bibr">[19]</xref>]. Multiple alignments of the whole protein sequences highlight a very high homology between the NC sequence of SARS-CoV-2 and bat RaTG13 CoV.</p><p id="p0095">This evidence does not reflect the overall genome alignments recently published where the draft whole-genome sequence of the pangolin coronavirus is clustered as the closest relative to SARS-CoV-2 [<xref rid="bib13" ref-type="bibr">13</xref>]. Our outcomes, instead, highlight a closer functional relationship between the bat RaTG13 and SARS-CoV-2 than the pair pangolin CoV and SARS-CoV-2 when restricting the investigation to a key structural protein. Also, NC protein of pangolin CoV fails to align two epitope sequences, suggesting a separation between the functional adaptation and molecular evolution. Moreover, acknowledged the overall co-share of epitope sequences, the lack of epitope alignments might be of importance for an accurate elucidation of the role of pangolin as the intermediate host in the virus life cycle.</p><p id="p0100">With regard to epitopes distribution across viruses with tropism for synanthropic and/or domestic animals, the survey highlights that some epitope sequences are more “conserved” among the most related specimens, while other epitopes are shared among a wider ensemble of coronaviruses. Similar outcomes were also described for the spike proteins epitopes [<xref rid="bib20" ref-type="bibr">20</xref>]. In this view, a detailed description of the epitopes distribution over the viral population might provide valuable information driving future researches aimed at setting efficient prophylactic strategies and/or the design of tool capable of differential diagnosis on the basis of serological tests.</p><p id="p0105">The adjacent mapping of the tested epitopes in the tridimensional models of the NC protein domains suggest the mapped area as being highly immunogenic, exposed to the solvent and, consequently, to molecular immune system effectors. Furthermore, this supports the immunogenicity of the selected epitope sequences which is of particular interest for that sequences scoring a lower level of identity in relation to SARS-CoV-2 such as the canine CoV, bovine CoV and the human enteric CoV. Although featured by a lower level of homology with SARS-CoV-2 NC protein and the presence of some mismatches in the epitope sequence, these sequences are mapping in the same structural domains as SARS-CoV-2 epitopes and are likely to be recognized by the host immune system; thus, potentially involved in conferring partial protection against SARS-CoV-2 infection other being considered good candidates for the development of diagnostic tools and prophylactic-oriented strategies.</p><p id="p0110">To conclude, COVID-19 pandemic is a global issue that stimulates the synergistic cooperation between research groups all over the world. At the same manner, planning studies that seek to address multiple aspects of COVID-19 enable a fast and effective control of the SARS-CoV-2 infections. In line with the One-Health concept, extending the target of the studies to the environment and the animals which humans are continuously interacting with favor a better understanding of this complex phenomenon and help to adopt the most suitable containment measures. Continuing mapping the major epitopes known for the viral proteins is, in our view, a promising strategy. In this light, defining the map of the circulating epitopes among diverse geographical areas and considering the diverse people habits and animal population they are interacting with might also provide unevaluable information for the design of personalized prophylactic and diagnostic strategies, shaped in dependence of the geographical context and the subject’s habits. Thus, an incisive focus on these aspects can contribute to a relatively fast control of this pandemic issue.</p></sec><sec id="sec5"><title>Conflict of interest</title><p id="p0050h">The authors declare no conflict on interest.</p></sec></body><back><ref-list id="cebib0010"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="journal" id="sref1"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>X.</given-names></name><name><surname>Wu</surname><given-names>Z.</given-names></name><name><surname>Yu</surname><given-names>R.</given-names></name><name><surname>Cao</surname><given-names>S.</given-names></name><name><surname>Fang</surname><given-names>W.</given-names></name><name><surname>Jiang</surname><given-names>Z.</given-names></name></person-group><article-title>Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak</article-title><source>MedRxiv</source><year>2020</year><comment>[Online ahead of print]. 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Cell host microbe</chapter-title><year>2020</year><comment>[Online ahead of print]</comment></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sref20"><person-group person-group-type="author"><name><surname>Tilocca</surname><given-names>B.</given-names></name><name><surname>Soggiu</surname><given-names>A.</given-names></name><name><surname>Musella</surname><given-names>V.</given-names></name><name><surname>Britti</surname><given-names>D.</given-names></name><name><surname>Sanguinetti</surname><given-names>M.</given-names></name><name><surname>Urbani</surname><given-names>A.</given-names></name></person-group><article-title>Molecular basis of COVID-19 relationships in different species: a one health perspective</article-title><source>Microbes Infect</source><year>2020</year><comment>[Epub ahead of print]</comment></element-citation></ref></ref-list><sec id="appsec1" sec-type="supplementary-material"><label>Appendix A</label><title>Supplementary data</title><p id="p0115">The following is the Supplementary data to this article:<supplementary-material content-type="local-data" id="mmc1"><caption><title>Multimedia component 1</title></caption><media xlink:href="mmc1.csv"><alt-text>Multimedia component 1</alt-text></media></supplementary-material></p></sec><fn-group><fn id="appsec2" fn-type="supplementary-material"><label>Appendix A</label><p id="p0120">Supplementary data to this article can be found online at <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/j.micinf.2020.04.002" id="intref0025">https://doi.org/10.1016/j.micinf.2020.04.002</ext-link>.</p></fn></fn-group></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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