{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:54:29Z","timestamp":1760234069836,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T00:00:00Z","timestamp":1616112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Human placenta formation relies on the interaction between fused trophoblast cells of the embryo with uterine endometrium. The fusion between trophoblast cells, first into cytotrophoblast and then into syncytiotrophoblast, is facilitated by the fusogenic protein syncytin. Syncytin derives from an envelope glycoprotein (ENV) of retroviral origin. In exogenous retroviruses, the envelope glycoproteins coded by env genes allow fusion of the viral envelope with the host cell membrane and entry of the virus into a host cell. During mammalian evolution, the env genes have been repeatedly, and independently, captured by various mammalian species to facilitate the formation of the placenta. Such a shift in the function of a gene, or a trait, for a different purpose during evolution is called an exaptation (co-option). We discuss the structure and origin of the placenta, the fusogenic and non-fusogenic functions of syncytin, and the mechanism of cell fusion. We also comment on an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin and the SARS-CoV-2 spike protein.<\/jats:p>","DOI":"10.3390\/biology10030238","type":"journal-article","created":{"date-parts":[[2021,3,19]],"date-time":"2021-03-19T11:18:38Z","timestamp":1616152718000},"page":"238","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Exaptation of Retroviral Syncytin for Development of Syncytialized Placenta, Its Limited Homology to the SARS-CoV-2 Spike Protein and Arguments against Disturbing Narrative in the Context of COVID-19 Vaccination"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5192-8584","authenticated-orcid":false,"given":"Malgorzata","family":"Kloc","sequence":"first","affiliation":[{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"MD Anderson Cancer Center, Department of Genetics, University of Texas, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Uosef","sequence":"additional","affiliation":[{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-5127","authenticated-orcid":false,"given":"Jacek Z.","family":"Kubiak","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), 01-163 Warsaw, Poland"},{"name":"Cell Cycle Group, Faculty of Medicine, Institute of Genetics and Development of Rennes (IGDR), University Rennes, CNRS, UMR 6290, 35043 Rennes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafik M.","family":"Ghobrial","sequence":"additional","affiliation":[{"name":"Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R179","DOI":"10.1530\/REP-16-0325","article-title":"The Evolution of the Placenta","volume":"152","author":"Roberts","year":"2016","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/jmor.20272","article-title":"Evolution of vertebrate viviparity and specializations for fetal nutrition: A quantitative and qualitative analysis","volume":"276","author":"Blackburn","year":"2015","journal-title":"J. Morphol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/icb\/32.2.276","article-title":"Reflections on the Evolution of Piscine Viviparity","volume":"32","author":"Wourms","year":"1992","journal-title":"Am. Zool."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/jez.1402660504","article-title":"Uterogestation and Placentation in Elasmobranchs","volume":"266","author":"Hamlett","year":"1993","journal-title":"J. Exp. Zool."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/j.1095-8649.2002.tb02490.x","article-title":"Functional significance of the male brood pouch in the reproductive strategies of pipefishes and seahorses: A morphological and ultrastructural comparative study on three anatomically different pouches","volume":"61","author":"Carcupino","year":"2002","journal-title":"J. Fish Biol."},{"key":"ref_6","unstructured":"Savage, J.M. (2002). The Amphibians and Reptiles of Costa Rica: A Herpetofauna between Two Continents, between Two Seas, University of Chicago Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mod.2017.12.002","article-title":"The extraordinary biology and development of marsupial frogs (Hemiphractidae) in comparison with fish, mammals, birds, amphibians and other animals","volume":"154","year":"2018","journal-title":"Mech. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/978-3-030-23459-1_16","article-title":"Embryogenesis of Marsupial Frogs (Hemiphractidae), and the Changes that Accompany Terrestrial Development in Frogs","volume":"68","year":"2019","journal-title":"Results Probl. Cell Differ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/jez.b.22632","article-title":"Placental specializations in lecithotrophic viviparous squamate reptiles","volume":"324","author":"Stewart","year":"2015","journal-title":"J. Exp. Zool. Part B Mol. Dev. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jmor.11011","article-title":"Invasive implantation and intimate placental associations in a placentotrophic african lizard, Trachylepis ivensi (scincidae)","volume":"273","author":"Blackburn","year":"2012","journal-title":"J. Morphol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S1095-6433(02)00188-5","article-title":"Energy and nutrient utilisation by embryonic reptiles","volume":"133","author":"Thompson","year":"2002","journal-title":"Comp. Biochem. Physiol. Part A\u2014Mol. Integr. Physiol."},{"key":"ref_12","unstructured":"Enders, A.C. (1981). Anatomy of the placenta and its relationship to function. Mead Johnson Symp. Perinat. Dev. Med., 3\u20137. Available online: https:\/\/europepmc.org\/article\/med\/6210810."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1136\/jcp.2008.055277","article-title":"The anatomy of the normal placenta","volume":"61","author":"Huppertz","year":"2008","journal-title":"J. Clin. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1016\/j.placenta.2009.12.023","article-title":"Review: Marsupials: Placental mammals with a difference","volume":"31","author":"Renfree","year":"2010","journal-title":"Placenta"},{"key":"ref_15","unstructured":"Austin, C.R., and Short, R.V. (1982). Implantation and Placentation Vol 2, Reproduction in Mammals: Embryonic and Fetal Development, Cambridge University Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0143-4004(92)90025-O","article-title":"Current topic: The synepitheliochorial placenta of ruminants: Binucleate cell fusions and hormone production","volume":"13","author":"Wooding","year":"1992","journal-title":"Placenta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.placenta.2004.01.011","article-title":"What can comparative studies of placental structure tell us?\u2013A review","volume":"25","author":"Enders","year":"2004","journal-title":"Placenta"},{"key":"ref_18","unstructured":"Funk, M. (2018). Identification and Characterization of Two Novel Syncytin-Like Retroviral Envelope Genes, Captured for a Possible role in the Atypical Structure of the Hyena Placenta and in the Emergence of the Non-Mammalian Mabuya Lizard Placenta a. Virology, Universit\u00e9 Paris Saclay (COmUE). \u2329NNT: 2018SACLS106\u232a."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e01811-18","DOI":"10.1128\/JVI.01811-18","article-title":"Capture of a Hyena-Specific Retroviral Envelope Gene with Placental Expression Associated in Evolution with the Unique Emergence among Carnivorans of Hemochorial Placentation in Hyaenidae","volume":"93","author":"Funk","year":"2019","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1073\/pnas.0511344103","article-title":"Evolution of the mammalian placenta revealed by phylogenetic analysis","volume":"103","author":"Wildman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1095\/biolreprod27.5.1247","article-title":"Placental Transport and Distribution of Uteroferrin in the Fetal","volume":"27","author":"Renegar","year":"1982","journal-title":"Pig. Biol. Reprod."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20120507","DOI":"10.1098\/rstb.2012.0507","article-title":"Paleovirology of \u2018syncytins\u2019, retroviral env genes exapted for a role in placentation","volume":"368","author":"Lavialle","year":"2013","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000337126","article-title":"The evolutionary dynamics of transposable elements in eukaryote genomes","volume":"7","author":"Tollis","year":"2010","journal-title":"Genome Dyn."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/978-1-61779-582-4_12","article-title":"Transposable elements and their identification","volume":"855","author":"Makalowski","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_25","unstructured":"Kurth, R., and Bannert, N. (2010). Retroviruses: Molecular Biology, Genomics and Pathogenesis, Horizon Scientific."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-virology-110615-035556","article-title":"The Discovery of Reverse Transcriptase","volume":"3","author":"Coffin","year":"2016","journal-title":"Annu. Rev. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-virology-100114-055043","article-title":"Retroviral Integrase: Then and Now","volume":"2","author":"Andrake","year":"2015","journal-title":"Annu. Rev. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.3390\/v2051181","article-title":"Special Issue: Retroviral Enzyme","volume":"2","year":"2010","journal-title":"Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10414","DOI":"10.1128\/JVI.77.19.10414-10422.2003","article-title":"Survey of human genes of retroviral origin: Identification and transcriptome of the genes with coding capacity for complete envelope proteins","volume":"77","author":"Lazar","year":"2003","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1742-4690-1-32","article-title":"Identification of endogenous retroviral reading frames in the human genome","volume":"1","author":"Villesen","year":"2004","journal-title":"Retrovirology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1128\/JVI.74.7.3321-3329.2000","article-title":"An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor","volume":"74","author":"Blond","year":"2000","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/35001608","article-title":"Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis","volume":"403","author":"Mi","year":"2000","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13013","DOI":"10.1073\/pnas.2132646100","article-title":"Genomewide screening for fusogenic human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution","volume":"100","author":"Blaise","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.bbrc.2005.04.032","article-title":"Structural characterization of the fusion core in syncytin, envelope protein of human endogenous retrovirus family W","volume":"331","author":"Gong","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17532","DOI":"10.1073\/pnas.0807413105","article-title":"A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2","volume":"105","author":"Esnault","year":"2008","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cohen, M. (2016). The Dark Side of Cell Fusion. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050638"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"de Parseval, N., Diop, G., Blaise, S., Helle, F., Vasilescu, A., Matsuda, F., and Heidmann, T. (2005). Comprehensive search for intra- and inter-specific sequence polymorphisms among coding envelope genes of retroviral origin found in the human genome: Genes and pseudogenes. BMC Genom., 6.","DOI":"10.1186\/1471-2164-6-117"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1073\/pnas.0406509102","article-title":"Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae","volume":"102","author":"Dupressoir","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100214","DOI":"10.1016\/j.bonr.2019.100214","article-title":"Role of the captured retroviral envelope syncytin-B gene in the fusion of osteoclast and giant cell precursors and in bone resorption, analyzed ex vivo and in vivo in syncytin-B knockout mice","volume":"11","author":"Coudert","year":"2019","journal-title":"Bone Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1095\/biolreprod.114.124818","article-title":"The captured retroviral envelope syncytin-A and syncytin-B genes are conserved in the Spalacidae together with hemotrichorial placentation","volume":"91","author":"Vernochet","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12127","DOI":"10.1073\/pnas.0902925106","article-title":"Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene","volume":"106","author":"Dupressoir","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E1164","DOI":"10.1073\/pnas.1112304108","article-title":"A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast","volume":"108","author":"Dupressoir","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"P13","DOI":"10.1186\/1742-4690-8-S2-P13","article-title":"Identification of syncytin-car-1, an endogenous retroviral envelope gene involved in placentation and conserved in Carnivora: A syncytin in a new superorder of placental mammals","volume":"8","author":"Cornelis","year":"2011","journal-title":"Retrovirology"},{"key":"ref_44","first-page":"E828","article-title":"A captured syncytin in Ruminantia","volume":"110","author":"Cornelis","year":"2013","journal-title":"PANAS"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1742-4690-6-107","article-title":"Identification of an endogenous retroviral envelope gene with fusogenic activity and placenta-specific expression in the rabbit: A new \u201csyncytin\u201d in a third order of mammals","volume":"6","author":"Heidmann","year":"2009","journal-title":"Retrovirology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7915","DOI":"10.1128\/JVI.00141-14","article-title":"Capture of syncytin-Mar1, a Fusogenic Endogenous Retroviral Envelope Gene Involved in Placentation in the Rodentia Squirrel-Related Clade","volume":"88","author":"Redelsperger","year":"2014","journal-title":"J. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1007\/s10815-014-0224-1","article-title":"Syncytin-1 and its receptor is present in human gametes","volume":"31","author":"Bjerregaard","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"R167","DOI":"10.1530\/REP-16-0031","article-title":"The role of syncytins in human reproduction and reproductive organ cancers","volume":"152","author":"Soygur","year":"2016","journal-title":"Reproduction"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/humrep\/dey340","article-title":"JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation","volume":"34","author":"Jean","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Clark, T. (2018). HAP2\/GCS1: Mounting evidence of our true biological EVE?. PLoS Biol., 20.","DOI":"10.1371\/journal.pbio.3000007"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fedry, J., Forcina, J., Legrand, P., P\u00e9hau-Arnaudet, G., Haouz, A., Johnson, M., Rey, F.A., and Krey, T. (2018). Evolutionary diversificationof the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006357"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1100\/tsw.2007.212","article-title":"Syncytin and Cancer Cell Fusions","volume":"7","author":"Larsson","year":"2007","journal-title":"Sci. World J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.humpath.2006.10.018","article-title":"Prognostic role of syncytin expression in breast cancer","volume":"38","author":"Larsson","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1083\/jcb.201901017","article-title":"How cell fuse","volume":"218","author":"Brukman","year":"2019","journal-title":"J. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.devcel.2007.12.008","article-title":"Viral and developmental cell fusion mechanisms: Conservation and divergence","volume":"14","author":"Sapir","year":"2008","journal-title":"Dev. Cell."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/humupd\/dmh039","article-title":"Syncytin: The major regulator of trophoblast fusion? Recent developments and hypotheses on its action","volume":"10","author":"Drewlo","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-94-007-0763-4_4","article-title":"Molecular and cellular mechanisms of mammalian cell fusion","volume":"713","author":"Zhou","year":"2011","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_58","first-page":"167","article-title":"The fusion pore, Biochimica et Biophysica Acta (BBA)","volume":"641","author":"Lindau","year":"2003","journal-title":"Mol. Cell Res."},{"key":"ref_59","first-page":"183","article-title":"Human Endogenous Retroviruses as Pathogenic Factors in the Development of Schizophrenia","volume":"6","author":"Slokar","year":"2015","journal-title":"Front. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/sj.mp.4001439","article-title":"HERV-W-related RNA detected in plasma from individuals with recent-onset schizophrenia or schizoaffective disorder","volume":"9","author":"Karlsson","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1742-4690-6-37","article-title":"Analysis of transcribed human endogenous retrovirus W env loci clarifies the origin of multiple sclerosis-associated retrovirus env sequences","volume":"6","author":"Laufer","year":"2009","journal-title":"Retrovirology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.bbi.2017.09.009","article-title":"Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells","volume":"67","author":"Wang","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fpsyt.2018.00422","article-title":"Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00705-002-0960-x","article-title":"The envelope glycoprotein of human endogenous retrovirus HERV-W induces cellular resistance to spleen necrosis virus","volume":"148","author":"Ponferrada","year":"2003","journal-title":"Arch. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1128\/JVI.73.2.1175-1185.1999","article-title":"Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family","volume":"73","author":"Blond","year":"1999","journal-title":"J. Virol."},{"key":"ref_66","first-page":"185","article-title":"Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells\u2020","volume":"102","author":"Lokossou","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_67","first-page":"43","article-title":"Vaccines for COVID-19: The current state of play","volume":"35","author":"Koirala","year":"2020","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41577-020-00480-0","article-title":"Viral targets for vaccines against COVID-19","volume":"21","author":"Dai","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1126\/science.abb2762","article-title":"Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2","volume":"367","author":"Yan","year":"2020","journal-title":"Science"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.imlet.2020.06.002","article-title":"How nicotine can inhibit cytokine storm in the lungs and prevent or lessen the severity of COVID-19 infection?","volume":"224","author":"Kloc","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13","DOI":"10.29245\/2578-3009\/2020\/2.1189","article-title":"SARS-CoV-2 subversion of the antiviral interferon alfa-response of lung macrophages","volume":"4","author":"Kloc","year":"2020","journal-title":"J. Immunol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1159\/000508560","article-title":"The role of genetic sex and mitochondria in response to COVID-19 infection","volume":"181","author":"Kloc","year":"2020","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_73","unstructured":"(2021, March 18). Available online: https:\/\/www.uniprot.org\/uniprot\/Q9UQF0#sequences."},{"key":"ref_74","unstructured":"(2021, March 18). Available online: https:\/\/www.uniprot.org\/uniprot\/P0DTC2#sequences."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1476-7961-7-9","article-title":"Value of eight-amino-acid matches in predicting the allergenicity status of proteins: An empirical bioinformatic investigation","volume":"7","author":"Herman","year":"2009","journal-title":"Clin. Mol. Allergy"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S1473-3099(20)30638-1","article-title":"Inclusion of pregnant women in COVID-19 vaccine development","volume":"20","author":"Heath","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Stafford, I.A., Parchem, J.G., and Sibai, B.M. (2021). The coronavirus disease 2019 vaccine in pregnancy: Risks, benefits, and recommendations. Am. J. Obstet. Gynecol.","DOI":"10.1016\/j.ajog.2021.01.022"},{"key":"ref_78","unstructured":"(2021, March 18). Available online: https:\/\/www.uchicagomedicine.org\/forefront\/coronavirus-disease-covid-19\/mrna-covid-19-vaccine-pregnancy-breastfeeding."},{"key":"ref_79","unstructured":"(2021, March 18). Available online: https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/vaccines\/recommendations\/pregnancy.html."},{"key":"ref_80","unstructured":"(2021, March 18). Available online: https:\/\/www.acog.org\/covid-19\/covid-19-vaccines-and-pregnancy-conversation-guide-for-clinicians."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/3\/238\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:38:04Z","timestamp":1760161084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/10\/3\/238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,19]]},"references-count":80,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["biology10030238"],"URL":"https:\/\/doi.org\/10.3390\/biology10030238","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2021,3,19]]}}}