{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:19:26Z","timestamp":1791357566722,"version":"4.3.1"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Projects of the Ministry of Science and Technology of China","award":["2021YFC2301300"],"award-info":[{"award-number":["2021YFC2301300"]}]},{"name":"National Key Research and Development Projects of the Ministry of Science and Technology of China","award":["32070528"],"award-info":[{"award-number":["32070528"]}]},{"name":"National Key Research and Development Projects of the Ministry of Science and Technology of China","award":["32270437"],"award-info":[{"award-number":["32270437"]}]},{"name":"National Natural Science Foundation of China","award":["2021YFC2301300"],"award-info":[{"award-number":["2021YFC2301300"]}]},{"name":"National Natural Science Foundation of China","award":["32070528"],"award-info":[{"award-number":["32070528"]}]},{"name":"National Natural Science Foundation of China","award":["32270437"],"award-info":[{"award-number":["32270437"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The continuous evolution of SARS-CoV-2 and the emergence of novel variants with numerous mutations have heightened concerns surrounding the possibility of cross-species transmission and the establishment of natural animal reservoirs for the virus, but the host range of emerging SARS-CoV-2 variants has not been fully explored yet. Methods: We employed an in vitro model comprising VSV\u2206G* pseudotyped viruses bearing SARS-CoV-2 spike proteins to explore the plausible host range of SARS-CoV-2 emerging variants. Results: The overall host tropism of emerging SARS-CoV-2 variants are consistent with that of the SARS-CoV-2 wuhan-hu-1 strain with minor difference. Pseudotyped viruses bearing spike protein from RaTG13 and RmYN02 can enter cell cultures from a broad range of mammalian species, revealing that mink and hamsters may act as potential intermediate hosts. We further investigated 95 potential site-specific mutations in the SARS-CoV-2 spike protein that could impact viral infectivity across different species. The results showed that 13 of these mutations notably increased the transduction rates by more than two-fold when compared to the wild-type spike protein. Further examination of these 13 mutations within cell cultures from 31 different species revealed heightened sensitivity in cells derived from palm civets, minks, and Chinese horseshoe bats to the VSV\u2206G*-SARS2-S mutants. Specific mutations, such as L24F, R158G, and L212I, were seen to significantly enhance the capacity for SARS-CoV-2 of cross-species transmission. Conclusions: This study offers critical insights for the ongoing surveillance and monitoring efforts of SARS-CoV-2 evolution, emphasizing the need for the vigilant monitoring of specific mutations in both human and animal populations.<\/jats:p>","DOI":"10.3390\/genes15101321","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T06:46:33Z","timestamp":1728888393000},"page":"1321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cross-Species Susceptibility of Emerging Variants of SARS-CoV-2 Spike"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2453-1821","authenticated-orcid":false,"given":"Meng","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lv","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingfen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1126\/science.abe5901","article-title":"Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans","volume":"371","author":"Sikkema","year":"2021","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41586-021-04353-x","article-title":"SARS-CoV-2 infection in free-ranging white-tailed deer","volume":"602","author":"Hale","year":"2022","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2114828118","DOI":"10.1073\/pnas.2114828118","article-title":"SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus)","volume":"118","author":"Chandler","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1038\/s41564-022-01268-9","article-title":"Divergent SARS-CoV-2 variant emerges in white-tailed deer with deer-to-human transmission","volume":"7","author":"Pickering","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41597-022-01543-8","article-title":"SARS-ANI: A global open access dataset of reported SARS-CoV-2 events in animals","volume":"9","author":"Nerpel","year":"2022","journal-title":"Sci. Data"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1038\/s41467-022-30698-6","article-title":"Transmission of SARS-CoV-2 from humans to animals and potential host adaptation","volume":"13","author":"Tan","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/mam.12225","article-title":"Risk of human-to-wildlife transmission of SARS-CoV-2","volume":"51","author":"Gryseels","year":"2021","journal-title":"Mamm. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/s41586-020-2180-5","article-title":"Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor","volume":"581","author":"Lan","year":"2020","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2020216118","DOI":"10.1073\/pnas.2020216118","article-title":"Cross-species recognition of SARS-CoV-2 to bat ACE2","volume":"118","author":"Liu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110558","DOI":"10.1016\/j.celrep.2022.110558","article-title":"Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants","volume":"38","author":"Zhang","year":"2022","journal-title":"Cell Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bate, N., Savva, C.G., Moody, P.C.E., Brown, E.A., Evans, S.E., Ball, J.K., Schwabe, J.W.R., Sale, J.E., and Brindle, N.P.J. (2022). In vitro evolution predicts emerging SARS-CoV-2 mutations with high affinity for ACE2 and cross-species binding. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010733"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","article-title":"SARS-CoV-2 variants, spike mutations and immune escape","volume":"19","author":"Harvey","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.chom.2022.01.006","article-title":"Mutations in SARS-CoV-2 variants of concern link to increased spike cleavage and virus transmission","volume":"30","author":"Escalera","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shuai, H., Chan, J.F., Yuen, T.T., Yoon, C., Hu, J.C., Wen, L., Hu, B., Yang, D., Wang, Y., and Hou, Y. (2021). Emerging SARS-CoV-2 variants expand species tropism to murines. EBioMedicine, 73.","DOI":"10.1016\/j.ebiom.2021.103643"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, L., Cui, Z., Li, Q., Wang, B., Yu, Y., Wu, J., Nie, J., Ding, R., Wang, H., and Zhang, Y. (2021). Ten emerging SARS-CoV-2 spike variants exhibit variable infectivity, animal tropism, and antibody neutralization. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02728-4"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41421-022-00431-0","article-title":"Broader-species receptor binding and structural bases of Omicron SARS-CoV-2 to both mouse and palm-civet ACE2s","volume":"8","author":"Li","year":"2022","journal-title":"Cell Discov."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41396-023-01368-2","article-title":"Comparative susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV across mammals","volume":"17","author":"Li","year":"2023","journal-title":"ISME J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5105","DOI":"10.1038\/s41467-023-40706-y","article-title":"Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer","volume":"14","author":"McBride","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2105253118","DOI":"10.1073\/pnas.2105253118","article-title":"SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection","volume":"118","author":"Bashor","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","first-page":"2033","article-title":"Establishing primary adult fibroblast cultures from rodents","volume":"44","author":"Seluanov","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.cell.2023.02.001","article-title":"A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike","volume":"186","author":"Dadonaite","year":"2023","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Singer, J., Gifford, R., Cotten, M., and Robertson, D. (Biol. Life Sci., 2020). CoV-GLUE: A Web Application for Tracking SARS-CoV-2 Genomic Variation, Biol. Life Sci., preprint.","DOI":"10.20944\/preprints202006.0225.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/j.cell.2020.07.012","article-title":"The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity","volume":"182","author":"Li","year":"2020","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jviromet.2010.04.017","article-title":"Real-time RT-qPCR assay for the analysis of human influenza A virus transcription and replication dynamics","volume":"168","author":"Vester","year":"2010","journal-title":"J. Virol. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jviromet.2007.02.007","article-title":"Quantitative multiplex assay for simultaneous detection of the Indiana serotype of vesicular stomatitis virus and HIV gag","volume":"143","author":"Coleman","year":"2007","journal-title":"J. Virol. Methods"},{"key":"ref_27","unstructured":"Case, D., Belfon, K., Ben-Shalom, I., Brozell, S., Cerutti, D., Cheatham, T., Cruzeiro, V., Darden, T., Duke, R., and Giambasu, G. (2020). AMBER 2020, University of California."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10482","DOI":"10.1021\/acs.jpclett.0c02958","article-title":"Computational insights into the conformational accessibility and binding strength of SARS-CoV-2 spike protein to human angiotensin-converting enzyme 2","volume":"11","author":"Peng","year":"2020","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99sb","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/s41392-021-00704-2","article-title":"N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding","volume":"6","author":"Niu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1016\/j.cell.2021.05.031","article-title":"Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species","volume":"184","author":"Liu","year":"2021","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization","volume":"596","author":"Planas","year":"2021","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102715","DOI":"10.1016\/j.jaut.2021.102715","article-title":"Evolutionary analysis of the Delta and Delta Plus variants of the SARS-CoV-2 viruses","volume":"124","author":"Kannan","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_36","first-page":"162","article-title":"SARS-CoV-2 variant biology: Immune escape, transmission and fitness","volume":"21","author":"Carabelli","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.gpb.2023.10.004","article-title":"RCoV19: A One-stop Hub for SARS-CoV-2 Genome Data Integration, Variant Monitoring, and Risk Pre-warning","volume":"21","author":"Li","year":"2023","journal-title":"Genom. Proteom. Bioinf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Bio."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1321\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:13:00Z","timestamp":1760112780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/10\/1321"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["genes15101321"],"URL":"https:\/\/doi.org\/10.3390\/genes15101321","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]}}}