{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:44:25Z","timestamp":1790765065949,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T00:00:00Z","timestamp":1610668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000277","name":"Department for Environment, Food and Rural Affairs, UK Government","doi-asserted-by":"publisher","award":["SE0557"],"award-info":[{"award-number":["SE0557"]}],"id":[{"id":"10.13039\/501100000277","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000277","name":"Department for Environment, Food and Rural Affairs, UK Government","doi-asserted-by":"publisher","award":["SV3700"],"award-info":[{"award-number":["SV3700"]}],"id":[{"id":"10.13039\/501100000277","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["871029"],"award-info":[{"award-number":["871029"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Ferrets were experimentally inoculated with SARS-CoV-2 (severe acute respiratory syndrome (SARS)-related coronavirus 2) to assess infection dynamics and host response. During the resulting subclinical infection, viral RNA was monitored between 2 and 21 days post-inoculation (dpi), and reached a peak in the upper respiratory cavity between 4 and 6 dpi. Viral genomic sequence analysis in samples from three animals identified the Y453F nucleotide substitution relative to the inoculum. Viral RNA was also detected in environmental samples, specifically in swabs of ferret fur. Microscopy analysis revealed viral protein and RNA in upper respiratory tract tissues, notably in cells of the respiratory and olfactory mucosae of the nasal turbinates, including olfactory neuronal cells. Antibody responses to the spike and nucleoprotein were detected from 21 dpi, but virus-neutralizing activity was low. A second intranasal inoculation (re-exposure) of two ferrets after a 17-day interval did not produce re-initiation of viral RNA shedding, but did amplify the humoral response in one animal. Therefore, ferrets can be experimentally infected with SARS-CoV-2 to model human asymptomatic infection.<\/jats:p>","DOI":"10.3390\/v13010113","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T02:36:05Z","timestamp":1611196565000},"page":"113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Intranasal Infection of Ferrets with SARS-CoV-2 as a Model for Asymptomatic Human Infection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-4265","authenticated-orcid":false,"given":"Helen E.","family":"Everett","sequence":"first","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7680-5110","authenticated-orcid":false,"given":"Fabian Z. X.","family":"Lean","sequence":"additional","affiliation":[{"name":"Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7448-8200","authenticated-orcid":false,"given":"Alexander M. P.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3514-3066","authenticated-orcid":false,"given":"Pauline M.","family":"van Diemen","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Bacteriology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9673-3684","authenticated-orcid":false,"given":"Joe","family":"James","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mollett","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien J.","family":"Coward","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Skinner","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Warren","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9078-6734","authenticated-orcid":false,"given":"Kevin R.","family":"Bewley","sequence":"additional","affiliation":[{"name":"National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Watson","sequence":"additional","affiliation":[{"name":"Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shellene","family":"Hurley","sequence":"additional","affiliation":[{"name":"Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8608-1144","authenticated-orcid":false,"given":"Kathryn A.","family":"Ryan","sequence":"additional","affiliation":[{"name":"National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yper","family":"Hall","sequence":"additional","affiliation":[{"name":"National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Simmons","sequence":"additional","affiliation":[{"name":"Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Pathology and Animal Sciences Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miles W.","family":"Carroll","sequence":"additional","affiliation":[{"name":"National Infection Service, Public Health England (PHE), Porton Down, Salisbury, Wiltshire SP4 0JG, UK"},{"name":"Nuffield Department of Medicine, Oxford University, Oxford OX1 3SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian H.","family":"Brown","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9207-6659","authenticated-orcid":false,"given":"Sharon M.","family":"Brookes","sequence":"additional","affiliation":[{"name":"Virology Department, Animal and Plant Health Agency, New Haw, Addlestone, Surrey KT15 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_2","unstructured":"WHO Coronavirus Disease (COVID-19) Dashboard, WHO. Available online: https:\/\/covid19.who.int\/?gclid=Cj0KCQjw6PD3BRDPARIsAN8pHuGW7gnuISkwhrrTFGyXHC9iezAHQb_uCFIkZk3p_5FFY4Wz81kkBHoaAiMqEALw_wcB."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Buitrago-Garcia, D., Egli-Gany, D., Counotte, M.J., Hossmann, S., Imeri, H., Ipekci, A.M., Salanti, G., and Low, N. (2020). Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLoS Med., 17.","DOI":"10.1101\/2020.04.25.20079103"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41579-018-0118-9","article-title":"Origin and evolution of pathogenic coronaviruses","volume":"17","author":"Cui","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Santini, J.M., and Edwards, S.J.L. (2020). Host range of SARS-CoV-2 and implications for public health. Lancet Microbe.","DOI":"10.1016\/S2666-5247(20)30069-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Irigoyen, N., Firth, A.E., Jones, J.D., Chung, B.Y., Siddell, S.G., and Brierley, I. (2016). High-resolution analysis of coronavirus gene expression by RNA sequencing and ribosome profiling. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005473"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kim, Y.I., Kim, S.G., Kim, S.M., Kim, E.H., Park, S.J., Yu, K.M., Chang, J.H., Kim, E.J., Lee, S., and Casel, M.A.B. (2020). Infection and rapid transmission of SARS-CoV-2 in ferrets. Cell Host Microbe.","DOI":"10.1016\/j.chom.2020.03.023"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shi, J., Wen, Z., Zhong, G., Yang, H., Wang, C., Huang, B., Liu, R., He, X., Shuai, L., and Sun, Z. (2020). Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2. Science.","DOI":"10.1101\/2020.03.30.015347"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sia, S.F., Yan, L.M., Chin, A.W.H., Fung, K., Choy, K.T., Wong, A.Y.L., Kaewpreedee, P., Perera, R., Poon, L.L.M., and Nicholls, J.M. (2020). Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature.","DOI":"10.21203\/rs.3.rs-20774\/v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.1038\/s41467-020-17367-2","article-title":"SARS-CoV-2 is transmitted via contact and via the air between ferrets","volume":"11","author":"Richard","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1056\/NEJMc2013400","article-title":"Transmission of SARS-CoV-2 in domestic cats","volume":"383","author":"Halfmann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1093\/cid\/ciaa644","article-title":"Simulation of the clinical and pathological manifestations of coronavirus disease 2019 (COVID-19) in a golden syrian hamster model: Implications for disease pathogenesis and transmissibility","volume":"71","author":"Chan","year":"2020","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/s41586-020-2324-7","article-title":"Respiratory disease in rhesus macaques inoculated with SARS-CoV-2","volume":"585","author":"Munster","year":"2020","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1126\/science.abb7314","article-title":"Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model","volume":"368","author":"Rockx","year":"2020","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s41590-020-00835-8","article-title":"Establishment of an African green monkey model for COVID-19","volume":"22","author":"Woolsey","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e218","DOI":"10.1016\/S2666-5247(20)30089-6","article-title":"SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: An experimental transmission study","volume":"1","author":"Schlottau","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16007","DOI":"10.1038\/s41598-020-72563-w","article-title":"Susceptibility of tree shrew to SARS-CoV-2 infection","volume":"10","author":"Zhao","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3074","DOI":"10.3201\/eid2612.202989","article-title":"Lack of susceptibility to SARS-CoV-2 and MERS-CoV in poultry","volume":"26","author":"Suarez","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2001005","DOI":"10.2807\/1560-7917.ES.2020.25.23.2001005","article-title":"SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020","volume":"25","author":"Oreshkova","year":"2020","journal-title":"Eurosurveillance"},{"key":"ref_21","unstructured":"ProMED (2020, June 29). Coronavirus Disease 2019 Update (281): Netherlands (North Brabant, Limburg) Farmed Mink, Spread, Animal, Global. Available online: https:\/\/promedmail.org\/promed-post\/?id=20200623.7502849."},{"key":"ref_22","unstructured":"ProMED (2020, June 29). Coronavirus Disease 2019 Update (284): Denmark (North Jutland) Animal, Farmed Mink, Spread, Dog. Available online: https:\/\/promedmail.org\/promed-post\/?id=7506728."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Oude Munnink, B.B., Sikkema, R.S., Nieuwenhuijse, D.F., Molenaar, R.J., Munger, E., Molenkamp, R., van der Spek, A., Tolsma, P., Rietveld, A., and Brouwer, M. (2020). Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science.","DOI":"10.1126\/science.abe5901"},{"key":"ref_24","unstructured":"OIE (2020, December 01). COVID-19 Portal. Available online: https:\/\/www.oie.int\/en\/scientific-expertise\/specific-information-and-recommendations\/questions-and-answers-on-2019novel-coronavirus\/events-in-animals\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41586-020-2787-6","article-title":"Animal models for COVID-19","volume":"586","author":"Dowling","year":"2020","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.virol.2007.12.032","article-title":"The SARS-CoV ferret model in an infection-challenge study","volume":"374","author":"Chu","year":"2008","journal-title":"Virology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41467-020-20439-y","article-title":"Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity","volume":"12","author":"Ryan","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1007\/BF01863914","article-title":"Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche","volume":"162","author":"Karber","year":"1931","journal-title":"Arch Exp. Path Pharmakol"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_30","first-page":"227","article-title":"The method of right and wrong cases (constant stimuli) without Gauss\u2019s formulae","volume":"2","author":"Spearman","year":"1908","journal-title":"Br. J. Psychol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02451-y"},{"key":"ref_32","unstructured":"Caly, L., Druce, J., Roberts, J., Bond, K., Tran, T., Kostecki, R., Yoga, Y., Naughton, W., Taiaroa, G., and Seemann, T. (2020). Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia. Med. J. Aust."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Corman, V.M., Landt, O., Kaiser, M., Molenkamp, R., Meijer, A., Chu, D.K., Bleicker, T., Br\u00fcnink, S., Schneider, J., and Schmidt, M.L. (2020). Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. Bull. Eur. Mal. Transm. Eur. Commun. Dis. Bull., 25.","DOI":"10.2807\/1560-7917.ES.2020.25.3.2000045"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lewandowski, K., Xu, Y., Pullan, S.T., Lumley, S.F., Foster, D., Sanderson, N., Vaughan, A., Morgan, M., Bright, N., and Kavanagh, J. (2019). Metagenomic nanopore sequencing of influenza virus direct from clinical respiratory samples. J. Clin. Microbiol., 58.","DOI":"10.1128\/JCM.00963-19"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT multiple sequence alignment software version 7: Improvements in performance and usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular evolutionary genetics analysis across computing platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21894","DOI":"10.1038\/s41598-020-78949-0","article-title":"Development of immunohistochemistry and in situ hybridisation for the detection of SARS-CoV and SARS-CoV-2 in formalin-fixed paraffin-embedded specimens","volume":"10","author":"Lean","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bao, L., Deng, W., Gao, H., Xiao, C., Liu, J., Xue, J., Lv, Q., Liu, J., Yu, P., and Xu, Y. (2020). Lack of reinfection in RHESUS Macaques Infected with SARS-CoV-2. bioRxiv.","DOI":"10.1101\/2020.03.13.990226"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jcpa.2014.01.004","article-title":"The pathology and pathogenesis of experimental severe acute respiratory syndrome and influenza in animal models","volume":"151","author":"Haagmans","year":"2014","journal-title":"J. Comp. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22311","DOI":"10.1073\/pnas.2010146117","article-title":"Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates","volume":"117","author":"Damas","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00405-020-05965-1","article-title":"Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): A multicenter European study","volume":"277","author":"Lechien","year":"2020","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xydakis, M.S., Dehgani-Mobaraki, P., Holbrook, E.H., Geisthoff, U.W., Bauer, C., Hautefort, C., Herman, P., Manley, G.T., Lyon, D.M., and Hopkins, C. (2020). Smell and taste dysfunction in patients with COVID-19. Lancet Infect. Dis.","DOI":"10.1016\/S1473-3099(20)30293-0"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Tong, J.Y., Wong, A., Zhu, D., Fastenberg, J.H., and Tham, T. (2020). The prevalence of olfactory and gustatory dysfunction in COVID-19 patients: A systematic review and meta-analysis. Otolaryngol. Head Neck Surg.","DOI":"10.1177\/0194599820926473"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Meinhardt, J., Radke, J., Dittmayer, C., Franz, J., Thomas, C., Mothes, R., Laue, M., Schneider, J., Br\u00fcnink, S., and Greuel, S. (2020). Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat. Neurosci.","DOI":"10.1038\/s41593-020-00758-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"495","DOI":"10.2471\/BLT.20.253591","article-title":"Variant analysis of SARS-CoV-2 genomes","volume":"98","author":"Koyama","year":"2020","journal-title":"Bull. World Health Organ."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Baum, A., Fulton, B.O., Wloga, E., Copin, R., Pascal, K.E., Russo, V., Giordano, S., Lanza, K., Negron, N., and Ni, M. (2020). Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science.","DOI":"10.1126\/science.abd0831"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hayashi, T., Yaegashi, N., and Konishi, I. (2020). Effect of RBD mutation (Y453F) in spike glycoprotein of SARS-CoV-2 on neutralizing antibody affinity. bioRxiv.","DOI":"10.1101\/2020.11.27.401893"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.cell.2020.08.012","article-title":"Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding","volume":"182","author":"Starr","year":"2020","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Piplani, S., Singh, P.K., Winkler, D.A., and Petrovsky, N. (2020). In silico comparison of spike protein-ACE2 binding affinities across species; significance for the possible origin of the SARS-CoV-2 virus. arXiv.","DOI":"10.1038\/s41598-021-92388-5"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1038\/s41467-020-19808-4","article-title":"SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking changes in SARS-CoV-2 spike: Evidence that D614G increases infectivity of the COVID-19 virus","volume":"182","author":"Korber","year":"2020","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1126\/science.abe8499","article-title":"SARS-CoV-2 D614G variant exhibits enhanced replication ex vivo and earlier transmission in vivo","volume":"370","author":"Hou","year":"2020","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhou, B., Thao, T.T.N., Hoffmann, D., Taddeo, A., Ebert, N., Labroussaa, F., Pohlmann, A., King, J., Portmann, J., and Halwe, N.J. (2020). SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility. bioRxiv.","DOI":"10.1101\/2020.10.27.357558"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41541-020-00246-8","article-title":"Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein","volume":"5","author":"McAuley","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Long, Q.-X., Tang, X.-J., Shi, Q.-L., Li, Q., Deng, H.-J., Yuan, J., Hu, J.-L., Xu, W., Zhang, Y., and Lv, F.-J. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat. Med.","DOI":"10.1038\/s41591-020-0965-6"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Robbiani, D.F., Gaebler, C., Muecksch, F., Lorenzi, J.C.C., Wang, Z., Cho, A., Agudelo, M., Barnes, C.O., Gazumyan, A., and Finkin, S. (2020). Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature.","DOI":"10.1038\/s41586-020-2456-9"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kutter, J.S., de Meulder, D., Bestebroer, T.M., Lexmond, P., Mulders, A., Fouchier, R.A., and Herfst, S. (2020). SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance. bioRxiv.","DOI":"10.21203\/rs.3.rs-93725\/v1"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1001\/jama.2020.3227","article-title":"Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) from a symptomatic patient","volume":"323","author":"Ong","year":"2020","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1056\/NEJMe2009758","article-title":"Asymptomatic transmission, the achilles\u2019 heel of current strategies to control Covid-19","volume":"382","author":"Gandhi","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/113\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:11:45Z","timestamp":1760159505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/113"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,15]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010113"],"URL":"https:\/\/doi.org\/10.3390\/v13010113","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,15]]}}}