Cross-Species Susceptibility of Emerging Variants of SARS-CoV-2 Spike.

Meng Li, Fei Lv, Zihao Li, Chenyu Zhao, Xiao Wang, Pingfen Zhu, Xuming Zhou
Author Information
  1. Meng Li: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ORCID
  2. Fei Lv: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  3. Zihao Li: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  4. Chenyu Zhao: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  5. Xiao Wang: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  6. Pingfen Zhu: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  7. Xuming Zhou: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

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���G* 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���G*-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.

Keywords

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Grants

  1. 2021YFC2301300/National Key Research and Development Projects of the Ministry of Science and Technology of China

MeSH Term

Spike Glycoprotein, Coronavirus
SARS-CoV-2
Animals
Humans
COVID-19
Host Specificity
Mutation
Cricetinae
Mink
Viral Tropism
Chiroptera
Rats

Chemicals

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Word Cloud

Created with Highcharts 10.0.0SARS-CoV-2mutationsspikevariantsproteincross-speciestransmissionhostrangeemergingspeciesevolutionheightenedanimalvirusesbearingcellculturespotentialviralinfectivitydifferent13monitoringBACKGROUND:continuousemergencenovelnumerousconcernssurroundingpossibilityestablishmentnaturalreservoirsvirusfullyexploredyetMETHODS:employedvitromodelcomprisingVSV���G*pseudotypedproteinsexploreplausibleRESULTS:overalltropismconsistentwuhan-hu-1strainminordifferencePseudotypedRaTG13RmYN02canenterbroadmammalianrevealingminkhamstersmayactintermediatehostsinvestigated95site-specificimpactacrossresultsshowednotablyincreasedtransductionratestwo-foldcomparedwild-typeexaminationwithin31revealedsensitivitycellsderivedpalmcivetsminksChinesehorseshoebatsVSV���G*-SARS2-SmutantsSpecificL24FR158GL212IseensignificantlyenhancecapacityCONCLUSIONS:studyofferscriticalinsightsongoingsurveillanceeffortsemphasizingneedvigilantspecifichumanpopulationsCross-SpeciesSusceptibilityEmergingVariantsSpike

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