Matches in SemOpenAlex for { <https://semopenalex.org/work/W4282004166> ?p ?o ?g. }
- W4282004166 abstract "Abstract Background Rodents, such as mice, are vulnerable targets, and potential intermediate hosts, of SARS-CoV-2 variants of concern, including Alpha, Beta, Gamma, and Omicron. N501Y in the receptor-binding domain (RBD) of Spike protein is the key mutation dictating the mouse infectivity, on which the neighboring mutations within RBD have profound impacts. However, the impacts of mutations outside RBD on N501Y-mediated mouse infectivity remain to be explored. Results Herein, we report that two non-RBD mutations derived from mouse-adapted strain, Ins215KLRS in the N-terminal domain (NTD) and H655Y in the subdomain linking S1 to S2, enhance mouse infectivity in the presence of N501Y mutation, either alone or together. This is associated with increased interaction of Spike with mouse ACE2 and mutations-induced local conformation changes in Spike protein. Mechanistically, the H655Y mutation disrupts interaction with N657, resulting in a less tight loop that wraps the furin-cleavage finger; and the insertion of 215KLRS in NTD increases its intramolecular interaction with a peptide chain that interfaced with the RBD-proximal region of the neighboring protomer, leading to a more flexible RBD that facilitates receptor binding. Moreover, the Omicron Spike that contains Ins214EPE and H655Y mutations confer mouse infectivity > 50 times over the N501Y mutant, which could be effectively suppressed by mutating them back to wild type. Conclusions Collectively, our study sheds light on the cooperation between distant Spike mutations in promoting virus infectivity, which may undermine the high infectiousness of Omicron variants towards mice." @default.
- W4282004166 created "2022-06-13" @default.
- W4282004166 creator A5011263744 @default.
- W4282004166 creator A5011375904 @default.
- W4282004166 creator A5022408502 @default.
- W4282004166 creator A5032773676 @default.
- W4282004166 creator A5041300353 @default.
- W4282004166 creator A5052646625 @default.
- W4282004166 creator A5068379269 @default.
- W4282004166 creator A5074054433 @default.
- W4282004166 creator A5082088302 @default.
- W4282004166 creator A5084399793 @default.
- W4282004166 date "2022-06-05" @default.
- W4282004166 modified "2023-10-09" @default.
- W4282004166 title "Long-range enhancement of N501Y-endowed mouse infectivity of SARS-CoV-2 by the non-RBD mutations of Ins215KLRS and H655Y" @default.
- W4282004166 cites W1905652520 @default.
- W4282004166 cites W1984259198 @default.
- W4282004166 cites W2043133007 @default.
- W4282004166 cites W2202803785 @default.
- W4282004166 cites W2970099101 @default.
- W4282004166 cites W2995619590 @default.
- W4282004166 cites W3004280078 @default.
- W4282004166 cites W3004348779 @default.
- W4282004166 cites W3004896487 @default.
- W4282004166 cites W3010441732 @default.
- W4282004166 cites W3012696170 @default.
- W4282004166 cites W3021061361 @default.
- W4282004166 cites W3033190604 @default.
- W4282004166 cites W3045870925 @default.
- W4282004166 cites W3080868475 @default.
- W4282004166 cites W3092136311 @default.
- W4282004166 cites W3093810043 @default.
- W4282004166 cites W3096796090 @default.
- W4282004166 cites W3106150549 @default.
- W4282004166 cites W3108980364 @default.
- W4282004166 cites W3124428400 @default.
- W4282004166 cites W3124898903 @default.
- W4282004166 cites W3131287340 @default.
- W4282004166 cites W3133289585 @default.
- W4282004166 cites W3134133080 @default.
- W4282004166 cites W3138856383 @default.
- W4282004166 cites W3153235517 @default.
- W4282004166 cites W3156471302 @default.
- W4282004166 cites W3159935191 @default.
- W4282004166 cites W3162133013 @default.
- W4282004166 cites W3162135285 @default.
- W4282004166 cites W3169407541 @default.
- W4282004166 cites W3172207918 @default.
- W4282004166 cites W3180285023 @default.
- W4282004166 cites W3181668248 @default.
- W4282004166 cites W3183386301 @default.
- W4282004166 cites W3184101260 @default.
- W4282004166 cites W3192172700 @default.
- W4282004166 cites W3194954046 @default.
- W4282004166 cites W3198725881 @default.
- W4282004166 cites W3200572254 @default.
- W4282004166 cites W3202702853 @default.
- W4282004166 cites W3203433659 @default.
- W4282004166 cites W3207414082 @default.
- W4282004166 cites W3210018682 @default.
- W4282004166 cites W3213524488 @default.
- W4282004166 cites W4200480444 @default.
- W4282004166 cites W4205203038 @default.
- W4282004166 cites W4206898072 @default.
- W4282004166 cites W4210792795 @default.
- W4282004166 cites W4211018920 @default.
- W4282004166 cites W4214724710 @default.
- W4282004166 cites W4220938747 @default.
- W4282004166 cites W4221037810 @default.
- W4282004166 cites W4224241797 @default.
- W4282004166 cites W4224298002 @default.
- W4282004166 cites W4225314443 @default.
- W4282004166 cites W4225358271 @default.
- W4282004166 cites W4226353088 @default.
- W4282004166 cites W4280505955 @default.
- W4282004166 doi "https://doi.org/10.1186/s13062-022-00325-x" @default.
- W4282004166 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35658928" @default.
- W4282004166 hasPublicationYear "2022" @default.
- W4282004166 type Work @default.
- W4282004166 citedByCount "8" @default.
- W4282004166 countsByYear W42820041662022 @default.
- W4282004166 countsByYear W42820041662023 @default.
- W4282004166 crossrefType "journal-article" @default.
- W4282004166 hasAuthorship W4282004166A5011263744 @default.
- W4282004166 hasAuthorship W4282004166A5011375904 @default.
- W4282004166 hasAuthorship W4282004166A5022408502 @default.
- W4282004166 hasAuthorship W4282004166A5032773676 @default.
- W4282004166 hasAuthorship W4282004166A5041300353 @default.
- W4282004166 hasAuthorship W4282004166A5052646625 @default.
- W4282004166 hasAuthorship W4282004166A5068379269 @default.
- W4282004166 hasAuthorship W4282004166A5074054433 @default.
- W4282004166 hasAuthorship W4282004166A5082088302 @default.
- W4282004166 hasAuthorship W4282004166A5084399793 @default.
- W4282004166 hasBestOaLocation W42820041661 @default.
- W4282004166 hasConcept C104317684 @default.
- W4282004166 hasConcept C106358424 @default.
- W4282004166 hasConcept C143065580 @default.
- W4282004166 hasConcept C159047783 @default.
- W4282004166 hasConcept C181199279 @default.
- W4282004166 hasConcept C207583985 @default.