{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:14:44Z","timestamp":1760145284611,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"NSFC-MFST project (China\u2013Mongolia)","doi-asserted-by":"publisher","award":["32161143027"],"award-info":[{"award-number":["32161143027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have an abnormally hard outer shell (low M disorder, i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far has been found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2, especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 and later in Omicron, is associated with attenuation according to the Shell-Disorder Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.<\/jats:p>","DOI":"10.3390\/ijms25147537","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T15:27:20Z","timestamp":1720538840000},"page":"7537","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Comparative Experimental and Computational Study on the Nature of the Pangolin-CoV and COVID-19 Omicron"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1866-5241","authenticated-orcid":false,"given":"Lai","family":"Wei","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7299-5719","authenticated-orcid":false,"given":"Lihua","family":"Song","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0744-5243","authenticated-orcid":false,"given":"A. Keith","family":"Dunker","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-6521","authenticated-orcid":false,"given":"James A.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA"},{"name":"Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-0806","authenticated-orcid":false,"given":"Gerard Kian-Meng","family":"Goh","sequence":"additional","affiliation":[{"name":"Goh\u2019s BioComputing, Singapore 548957, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1126\/science.abp8715","article-title":"The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic","volume":"377","author":"Worobey","year":"2022","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1126\/science.abp8337","article-title":"The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2","volume":"377","author":"Pekar","year":"2022","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. 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