{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:30:46Z","timestamp":1773289846565,"version":"3.50.1"},"reference-count":109,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID\u2014percentage of intrinsic disorder\u2014of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles in the lungs and bronchial tissues, respectively, as there is a greater level of mucus in the bronchi. The other observation revealed that there are lower viral loads in 2017-pangolin-CoV, which is predicted to have similarly low PIDN as Omicron. The abnormally hard M, which is very rarely seen in coronaviruses, arose from the fecal\u2013oral behaviors of pangolins via exposure to buried feces. Pangolins provide an environment for coronavirus (CoV) attenuation, which is seen in Omicron. Phylogenetic study using M shows that COVID-19-related bat-CoVs from Laos and Omicron are clustered in close proximity to pangolin-CoVs, which suggests the recurrence of interspecies transmissions. Hard M may have implications for long COVID-19, with immune systems having difficulty degrading viral proteins\/particles.<\/jats:p>","DOI":"10.3390\/biom12101353","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"1353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Study on the Nature of SARS-CoV-2 Using the Shell Disorder Models: Reproducibility, Evolution, Spread, and Attenuation"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-0806","authenticated-orcid":false,"given":"Gerard Kian-Meng","family":"Goh","sequence":"first","affiliation":[{"name":"Goh\u2019s BioComputing, Singapore 548957, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Keith","family":"Dunker","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, Indiana and Bioinformatics, 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"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"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. Rev. Microbiol."},{"key":"ref_4","unstructured":"WHO (2022, August 16). Coronavirus Disease (COVID-19) Pandemic 2020. Available online: https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"E6","DOI":"10.1038\/s41586-020-2951-z","article-title":"Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"588","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/jmv.25731","article-title":"Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2","volume":"92","author":"Li","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41586-022-04532-4","article-title":"Bat coronaviruses related to SARS-CoV-2 and infectious for human cells","volume":"604","author":"Temmam","year":"2022","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11262-021-01846-9","article-title":"SARS coronavirus outbreaks past and present-a comparative analysis of SARS-CoV-2 and its predecessors","volume":"57","author":"Low","year":"2021","journal-title":"Virus Genes."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s41586-020-2313-x","article-title":"Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins","volume":"583","author":"Xiao","year":"2020","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41586-020-2169-0","article-title":"Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins","volume":"583","author":"Lam","year":"2020","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.cub.2020.03.022","article-title":"Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak","volume":"30","author":"Zhang","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1097\/CM9.0000000000000797","article-title":"Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus-related coronavirus model","volume":"133","author":"Fan","year":"2020","journal-title":"Chin. Med. J. (Engl.)"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"826116","DOI":"10.3389\/fpubh.2022.826116","article-title":"Evidence of SARS-CoV-2 Related Coronaviruses Circulating in Sunda pangolins (Manis javanica) Confiscated From the Illegal Wildlife Trade in Viet Nam","volume":"10","author":"Nga","year":"2022","journal-title":"Front. Public Health"},{"key":"ref_14","unstructured":"European_CDC (2022, August 14). European Center for Disease Prevention and Control, Weekly Epidemilogical Update: Omicron Variant of Concern (VOC). Available online: https:\/\/www.ecdc.europa.eu\/en\/news-events\/weekly-epidemiological-update-omicron-variant-concern-voc-week-2-data-20-january-2022."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0140-6736(22)00017-4","article-title":"Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: A data linkage study","volume":"399","author":"Wolter","year":"2022","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ijid.2021.12.357","article-title":"Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa","volume":"116","author":"Abdullah","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41577-022-00678-4","article-title":"Milder disease with Omicron: Is it the virus or the pre-existing immunity?","volume":"22","author":"Sigal","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1126\/science.acx9738","article-title":"Where did \u2018weird\u2019 Omicron come from?","volume":"374","author":"Kupferschmidt","year":"2021","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Moeller, N.H., Shi, K., Demir, O., Belica, C., Banerjee, S., Yin, L., Durfee, C., Amaro, R.E., and Aihara, H. (2022). Structure and dynamics of SARS-CoV-2 proofreading exoribonuclease ExoN. Proc. Natl. Acad. Sci. USA, 119.","DOI":"10.1073\/pnas.2106379119"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Tay, J.H., Porter, A.F., Wirth, W., and Duchene, S. (2022). The Emergence of SARS-CoV-2 Variants of Concern Is Driven by Acceleration of the Substitution Rate. Mol. Biol. Evol., 39.","DOI":"10.1093\/molbev\/msac013"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2022). Shell Disorder Models Detect That Omicron Has Harder Shells with Attenuation but Is Not a Descendant of the Wuhan-Hu-1 SARS-CoV-2. Biomolecules, 12.","DOI":"10.3390\/biom12050631"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1021\/acs.jproteome.2c00001","article-title":"Computational, Experimental, and Clinical Evidence of a Specific but Peculiar Evolutionary Nature of (COVID-19) SARS-CoV-2","volume":"21","author":"Goh","year":"2022","journal-title":"J. Proteome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1056\/NEJMc2031364","article-title":"Persistence and Evolution of SARS-CoV-2 in an Immunocompro0mised Host","volume":"383","author":"Choi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/1743-422X-5-126","article-title":"A comparative analysis of viral matrix proteins using disorder predictors","volume":"5","author":"Goh","year":"2008","journal-title":"Virol. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., and Uversky, V.N. (2008). Protein intrinsic disorder toolbox for comparative analysis of viral proteins. BMC Genom., 9.","DOI":"10.1186\/1471-2164-9-S2-S4"},{"key":"ref_26","unstructured":"Goh, G.K. (2017). Viral Shapeshifters: Strange Behaviors of HIV and Other Viruses, Simplicity Research Institute."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5702","DOI":"10.1080\/07391102.2020.1870562","article-title":"Shell disorder and the HIV vaccine mystery: Lessons from the legendary Oswald Avery","volume":"40","author":"Goh","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2019). HIV Vaccine Mystery and Viral Shell Disorder. Biomolecules, 9.","DOI":"10.3390\/biom9050178"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., and Uversky, V.N. (2012). Understanding Viral Transmission Behavior via Protein Intrinsic Disorder Prediction: Coronaviruses. J. Pathog., 2012.","DOI":"10.1155\/2012\/738590"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1039\/C5MB00240K","article-title":"Detection of links between Ebola nucleocapsid and virulence using disorder analysis","volume":"11","author":"Goh","year":"2015","journal-title":"Mol. Biosyst."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2019). Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity. Biomolecules, 9.","DOI":"10.3390\/biom9110710"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2020). Nipah shell disorder, modes of infection, and virulence. Microb. Pathog., 141.","DOI":"10.1016\/j.micpath.2020.103976"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1039\/C6MB00228E","article-title":"Correlating Flavivirus virulence and levels of intrinsic disorder in shell proteins: Protective roles vs. immune evasion","volume":"12","author":"Goh","year":"2016","journal-title":"Mol. Biosyst."},{"key":"ref_34","first-page":"143","article-title":"Feasibility of the vaccine development for SARS-CoV-2 and other viruses using the shell disorder analysis","volume":"26","author":"Goh","year":"2021","journal-title":"Pac. Symp. Biocomput."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1021\/acs.jproteome.0c00460","article-title":"Shell Disorder Analysis Suggests That Pangolins Offered a Window for a Silent Spread of an Attenuated SARS-CoV-2 Precursor among Humans","volume":"19","author":"Goh","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2020). Shell disorder analysis predicts greater resilience of the SARS-CoV-2 (COVID-19) outside the body and in body fluids. Microb. Pathog., 144.","DOI":"10.1016\/j.micpath.2020.104177"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., Foster, J.A., and Uversky, V.N. (2020). Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity. Biomolecules, 10.","DOI":"10.3390\/biom10020331"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/tbed.13707","article-title":"Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review","volume":"68","author":"Aboubakr","year":"2021","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1177\/0022034511399282","article-title":"Antiviral activities in human saliva","volume":"23","author":"Malamud","year":"2011","journal-title":"Adv. Dent. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1172\/JCI0215218","article-title":"Antimicrobial polypeptides in host defense of the respiratory tract","volume":"109","author":"Ganz","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1128\/IAI.67.7.3267-3275.1999","article-title":"Innate antimicrobial activity of nasal secretions","volume":"67","author":"Cole","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.36557\/2674-8169.2022v4n1p50-54","article-title":"HKUMed finds Omicron SARS-CoV-2 can infect faster and better than Delta in human bronchus but with less severe infection in lung","volume":"4","author":"Chan","year":"2022","journal-title":"Braz. J. Implantol. Health Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41586-022-04479-6","article-title":"SARS-CoV-2 Omicron variant replication in human bronchus and lung ex vivo","volume":"603","author":"Hui","year":"2022","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Guo, Z., Zhang, C., Zhang, C., Cui, H., Chen, Z., Jiang, X., Wang, T., Li, Y., Liu, J., and Wan, Z. (2022). SARS-CoV-2-related pangolin coronavirus exhibits similar infection characteristics to SARS-CoV-2 and direct contact transmissibility in hamsters. iScience, 25.","DOI":"10.1016\/j.isci.2022.104350"},{"key":"ref_45","unstructured":"Shanshan, L., Shengdong, L., Chang, L., Muli, L., Xiaoping, A., Mengzhe, L., Jun, H., Huahao, F., Panyong, M., and Tigang, T. (2022). A highly attenuated SARS-CoV-2 related pangolin coronavirus variant has a 104nt deletion at the 3\u2019-terminus untranslated region. bioRxiv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0169-5347(00)02027-9","article-title":"How does recombination affect phylogeny estimation?","volume":"15","author":"Posada","year":"2000","journal-title":"Trends Ecol. Evol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12964-022-00821-7","article-title":"Intrinsically disordered proteins play diverse roles in cell signaling","volume":"20","author":"Bondos","year":"2022","journal-title":"Cell Commun. Signal"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6614","DOI":"10.1021\/acs.chemrev.1c00848","article-title":"Intrinsically Disordered Proteins: Critical Components of the Wetware","volume":"122","author":"Kulkarni","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1146\/annurev-biophys-062920-063704","article-title":"Recent Developments in the Field of Intrinsically Disordered Proteins: Intrinsic Disorder-Based Emergence in Cellular Biology in Light of the Physiological and Pathological Liquid-Liquid Phase Transitions","volume":"50","author":"Uversky","year":"2021","journal-title":"Annu. Rev. Biophys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6589","DOI":"10.1021\/cr400525m","article-title":"Classification of intrinsically disordered regions and proteins","volume":"114","author":"Buljan","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1146\/annurev-biochem-072711-164947","article-title":"Intrinsically disordered proteins and intrinsically disordered protein regions","volume":"83","author":"Oldfield","year":"2014","journal-title":"Annu. Rev. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.bbapap.2012.12.008","article-title":"Unusual biophysics of intrinsically disordered proteins","volume":"1834","author":"Uversky","year":"2013","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.bbapap.2010.01.017","article-title":"Understanding protein non-folding","volume":"1804","author":"Uversky","year":"2010","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0022-2836(02)00969-5","article-title":"Intrinsic disorder in cell-signaling and cancer-associated proteins","volume":"323","author":"Iakoucheva","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S0968-0004(02)02169-2","article-title":"Intrinsically unstructured proteins","volume":"27","author":"Tompa","year":"2002","journal-title":"Trends Biochem. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1100\/tsw.2002.25","article-title":"The Protein Trinity: Structure\/Function Relationships That Include Intrinsic Disorder","volume":"2","author":"Dunker","year":"2002","journal-title":"ScientificWorldJournal"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6573","DOI":"10.1021\/bi012159+","article-title":"Intrinsic disorder and protein function","volume":"41","author":"Dunker","year":"2002","journal-title":"Biochemistry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1110\/ps.4210102","article-title":"Natively unfolded proteins: A point where biology waits for physics","volume":"11","author":"Uversky","year":"2002","journal-title":"Protein Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1046\/j.0014-2956.2001.02649.x","article-title":"What does it mean to be natively unfolded?","volume":"262","author":"Uversky","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S1093-3263(00)00138-8","article-title":"Intrinsically disordered protein","volume":"19","author":"Dunker","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1002\/1097-0134(20001115)41:3<415::AID-PROT130>3.0.CO;2-7","article-title":"Why are \u201cnatively unfolded\u201d proteins unstructured under physiologic conditions?","volume":"41","author":"Uversky","year":"2000","journal-title":"Proteins"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1006\/jmbi.1999.3110","article-title":"Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm","volume":"293","author":"Wright","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO;2-3","article-title":"Sequence complexity of disordered protein","volume":"42","author":"Romero","year":"2001","journal-title":"Proteins"},{"key":"ref_64","unstructured":"PONDR (2022, August 14). Predictor of Natural Disordered Regions. Available online: https:\/\/www.pondr.com."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1021\/acs.jproteome.0c00672","article-title":"A Novel Strategy for the Development of Vaccines for SARS-CoV-2 (COVID-19) and Other Viruses Using AI and Viral Shell Disorder","volume":"19","author":"Goh","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2174\/092986610791498984","article-title":"Viral disorder or disordered viruses: Do viral proteins possess unique features?","volume":"17","author":"Xue","year":"2010","journal-title":"Protein Pept. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1743-422X-6-69","article-title":"Protein intrinsic disorder and influenza virulence: The 1918 H1N1 and H5N1 viruses","volume":"6","author":"Goh","year":"2009","journal-title":"Virol. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13468","DOI":"10.1021\/bi7012273","article-title":"Mining alpha-helix-forming molecular recognition features with cross species sequence alignments","volume":"46","author":"Cheng","year":"2007","journal-title":"Biochemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1021\/pr0701411","article-title":"Characterization of molecular recognition features, MoRFs, and their binding partners","volume":"6","author":"Vacic","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.jmb.2006.07.087","article-title":"Analysis of molecular recognition features (MoRFs)","volume":"362","author":"Mohan","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12454","DOI":"10.1021\/bi050736e","article-title":"Coupled folding and binding with alpha-helix-forming molecular recognition elements","volume":"44","author":"Oldfield","year":"2005","journal-title":"Biochemistry"},{"key":"ref_72","first-page":"41","article-title":"Predicting Binding Regions within Disordered Proteins","volume":"10","author":"Garner","year":"1999","journal-title":"Genome Inf. Ser Workshop Genome Inf."},{"key":"ref_73","first-page":"30","article-title":"Predicting Protein Disorder for N-, C-, and Internal Regions","volume":"10","author":"Li","year":"1999","journal-title":"Genome Inf. Ser Workshop Genome Inf."},{"key":"ref_74","unstructured":"UniProt_Consortium (2021). UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res., 49, D480\u2013D489."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"D94","DOI":"10.1093\/nar\/gky989","article-title":"GenBank","volume":"47","author":"Sayers","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_76","unstructured":"(2022, August 14). MySQL. Available online: https:\/\/www.mysql.com."},{"key":"ref_77","unstructured":"(2022, August 14). JAVA: JAVA Programming Language. Available online: https:\/\/www.java.com."},{"key":"ref_78","unstructured":"(2022, August 14). EMBI-EBI: Clustal Omega. Available online: https:\/\/www.ebi.ac.uk\/Tools\/msa\/clustalo\/."},{"key":"ref_79","unstructured":"(2022, August 14). TREX: CLUSTALW. Available online: http:\/\/www.trex.uqam.ca\/index.php?action=align&project=trex."},{"key":"ref_80","unstructured":"(2022, August 14). GIMP: GNU Image Manipulator Program. Available online: https:\/\/www.gimp.org."},{"key":"ref_81","unstructured":"(2022, August 14). OpenOffice. Available online: https:\/\/www.openoffice.org\/."},{"key":"ref_82","unstructured":"(2022, August 14). NCBI-BLASTP, Available online: https:\/\/blast.ncbi.nlm.nih.gov\/Blast.cgi?PAGE=Proteins."},{"key":"ref_83","unstructured":"(2022, August 24). R: A Language and Environment for Statistical Computing. Available online: http:\/\/softlibre.unizar.es\/manuales\/aplicaciones\/r\/fullrefman.pdf."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Goh, G.K., Dunker, A.K., and Uversky, V. (2013). Prediction of Intrinsic Disorder in MERS-CoV\/HCoV-EMC Supports a High Oral-Fecal Transmission. PLoS Curr., 5.","DOI":"10.1371\/currents.outbreaks.22254b58675cdebc256dbe3c5aa6498b"},{"key":"ref_85","first-page":"1264","article-title":"Progress in researches on human coronavirus HKU1: A review","volume":"33","author":"Lei","year":"2017","journal-title":"Chin. J. Public Health"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/JVI.79.2.884-895.2005","article-title":"Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia","volume":"79","author":"Woo","year":"2005","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1674\/0003-0031(2001)146[0053:BABCBO]2.0.CO;2","article-title":"Burrows and burrow-cleaning behavior of house mice (Mus musculus domesticus)","volume":"146","author":"Drickamer","year":"2001","journal-title":"Am. Midl. Nat."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3390\/v6082991","article-title":"The coronavirus nucleocapsid is a multifunctional protein","volume":"6","author":"McBride","year":"2014","journal-title":"Viruses"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/aje.12759","article-title":"Pangolins and bats living together in underground burrows in Lope National Park, Gabon","volume":"58","author":"Lehmann","year":"2020","journal-title":"Afr. J. Ecol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1080\/07391102.2020.1821784","article-title":"Household pets and SARS-CoV2 transmissibility in the light of the ACE2 intrinsic disorder status","volume":"40","author":"Uversky","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Mire, C.E., Satterfield, B.A., Geisbert, J.B., Agans, K.N., Borisevich, V., Yan, L., Chan, Y.-P., Cross, R.W., Fenton, K.A., and Broder, C.C. (2016). Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in Primates: Implications for Antibody Therapy. Sci. Rep., 6.","DOI":"10.1038\/srep30916"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-020-2196-x","article-title":"Virological assessment of hospitalized patients with COVID-2019","volume":"581","author":"Wolfel","year":"2020","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1099\/jgv.0.001453","article-title":"SARS-coronavirus-2 replication in Vero E6 cells: Replication kinetics, rapid adaptation and cytopathology","volume":"101","author":"Ogando","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/frym.2019.00106","article-title":"Moving mucus matters for lung health","volume":"7","author":"Weupe","year":"2019","journal-title":"Front. Young Minds."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMra0910061","article-title":"Airway mucus function and dysfunction","volume":"363","author":"Fahy","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1111\/j.1445-5994.1984.tb04928.x","article-title":"Alveolar type I and type II cells","volume":"14","author":"Ward","year":"1984","journal-title":"Aust. N. Z. J. Med."},{"key":"ref_97","unstructured":"Abrahams, P. (2016). How the Body Works: A Comprehensive Illustrated Encyclopedia of Anatomy, Amber Books Ltd."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ijbiomac.2022.07.022","article-title":"An integrated understanding of the evolutionary and structural features of the SARS-CoV-2 spike receptor binding domain (RBD)","volume":"217","author":"Sanyal","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bbrc.2022.06.064","article-title":"SARS-CoV-2 Spike mutations modify the interaction between virus Spike and human ACE2 receptors","volume":"620","author":"Mishra","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Bayani, F., Hashkavaei, N.S., Uversky, V.N., Mozaffari-Jovin, S., and Sefidbakht, Y. (2022). Insights into the structural peculiarities of the N-terminal and receptor binding domains of the spike protein from the SARS-CoV-2 Omicron variant. Comput. Biol. Med., 147.","DOI":"10.1016\/j.compbiomed.2022.105735"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Piplani, S., Singh, P.K., Winkler, D.A., and Petrovsky, N. (2021). In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-92388-5"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hassan, S.S., Ghosh, S., Attrish, D., Choudhury, P.P., Aljabali, A.A.A., Uhal, B.D., Lundstrom, K., Rezaei, N., Uversky, V.N., and Seyran, M. (2020). Possible Transmission Flow of SARS-CoV-2 Based on ACE2 Features. Molecules, 25.","DOI":"10.1101\/2020.10.08.332452"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Elrashdy, F., Redwan, E.M., and Uversky, V.N. (2020). Intrinsic disorder perspective of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2. Infect. Genet. Evol., 85.","DOI":"10.1016\/j.meegid.2020.104510"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41586-020-2179-y","article-title":"Structural basis of receptor recognition by SARS-CoV-2","volume":"581","author":"Shang","year":"2020","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.jgg.2021.12.003","article-title":"Evidence for a mouse origin of the SARS-CoV-2 Omicron variant","volume":"48","author":"Wei","year":"2021","journal-title":"J. Genet. Genom."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12985-020-01418-7","article-title":"The effect of temperature on persistence of SARS-CoV-2 on common surfaces","volume":"17","author":"Riddell","year":"2020","journal-title":"Virol. J."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Hirose, R., Itoh, Y., Ikegaya, H., Miyazaki, H., Watanabe, N., Yoshida, T., Bandou, R., Daidoji, T., and Nakaya, T. (2022). Differences in environmental stability among SARS-CoV-2 variants of concern: Both omicron BA.1 and BA.2 have higher stability. Clin. Microbiol. Infect.","DOI":"10.1101\/2022.01.18.476607"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Jones, T.C., Biele, G., M\u00fchlemann, B., Veith, T., Schneider, J., Beheim-Schwarzbach, J., Bleicker, T., Tesch, J., Schmidt, M.L., and Sander, L.E. (2021). Estimating infectiousness throughout SARS-CoV-2 infection course. Science, 373.","DOI":"10.1126\/science.abi5273"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e13","DOI":"10.1016\/S2666-5247(20)30172-5","article-title":"SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis","volume":"2","author":"Cevik","year":"2021","journal-title":"Lancet Microbe"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1353\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:02Z","timestamp":1760143082000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/10\/1353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":109,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biom12101353"],"URL":"https:\/\/doi.org\/10.3390\/biom12101353","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}