{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:01:16Z","timestamp":1790841676414,"version":"4.1.0"},"reference-count":105,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends\/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.<\/jats:p>","DOI":"10.3390\/cells9122638","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T11:50:49Z","timestamp":1607428249000},"page":"2638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":181,"title":["Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-8985","authenticated-orcid":false,"given":"Ma\u2019mon M.","family":"Hatmal","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Health Sciences, The Hashemite University, Zarqa 13133, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-7328","authenticated-orcid":false,"given":"Walhan","family":"Alshaer","sequence":"additional","affiliation":[{"name":"Cell Therapy Center (CTC), The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-9519","authenticated-orcid":false,"given":"Mohammad A. I.","family":"Al-Hatamleh","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Hatmal","sequence":"additional","affiliation":[{"name":"Prince Hamza Hospital, Amman 11947, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9586-3743","authenticated-orcid":false,"given":"Othman","family":"Smadi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Engineering, The Hashemite University, Zarqa 13133, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-072X","authenticated-orcid":false,"given":"Mutasem O.","family":"Taha","sequence":"additional","affiliation":[{"name":"Drug Design and Discovery Unit, Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1256-4893","authenticated-orcid":false,"given":"Ayman J.","family":"Oweida","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-0627","authenticated-orcid":false,"given":"Jennifer C.","family":"Boer","sequence":"additional","affiliation":[{"name":"Translational Immunology and Nanotechnology Unit, School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-6421","authenticated-orcid":false,"given":"Rohimah","family":"Mohamud","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6889-3667","authenticated-orcid":false,"given":"Magdalena","family":"Plebanski","sequence":"additional","affiliation":[{"name":"Translational Immunology and Nanotechnology Unit, School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1128\/JVI.00127-20","article-title":"Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus","volume":"94","author":"Wan","year":"2020","journal-title":"J. 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