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1.
Cell ; 185(12): 2103-2115.e19, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35568035

RESUMO

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.


Assuntos
COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , COVID-19/virologia , Cricetinae , Células Epiteliais , Humanos , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/genética
2.
Biochim Biophys Acta ; 1725(3): 385-93, 2005 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-15978731

RESUMO

The binding of flunitrazepam (FNZP) by human alpha1-acid glycoprotein (hAGP) and the relationships between the extent of drug binding and desialylation and the genetic variants of hAGP were examined. The photolabeling specificity of [3H]FNZP was confirmed by findings in which other hAGP-binding ligands inhibited the formation of covalent bonds between [3H]FNZP and hAGP. The photolabeling of asialo-hAGP suggested that sialic acid does not involve in the binding of [3H]FNZP. No difference in the labeling could be found between the F1*S variants and A variant. Similarly, FNZP did not show a difference in binding affinity to the two genetic variants of hAGP. Sequence analysis of the photolabeled peptide indicated a sequence corresponding to Tyr91-Arg105 of hAGP.


Assuntos
Sítios de Ligação , Flunitrazepam/metabolismo , Orosomucoide/química , Marcadores de Fotoafinidade/metabolismo , Sequência de Aminoácidos , Assialoglicoproteínas/metabolismo , Brometo de Cianogênio , Variação Genética , Humanos , Dados de Sequência Molecular , Orosomucoide/análogos & derivados , Orosomucoide/genética , Orosomucoide/metabolismo , Fragmentos de Peptídeos/química , Tripsina
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