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1.
Proc Natl Acad Sci U S A ; 120(18): e2213332120, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: covidwho-2304032

RESUMEN

Among the current five Variants of Concern, infections caused by SARS-CoV-2 B.1.617.2 (Delta) variant are often associated with the greatest severity. Despite recent advances on the molecular basis of elevated pathogenicity using recombinant proteins, the architecture of intact Delta virions remains veiled. Moreover, pieces of molecular evidence for the detailed mechanism of S-mediated membrane fusion are missing. Here, we showed the pleomorphic nature of Delta virions from electron beam inactivated samples and reported the in situ structure and distribution of S on the authentic Delta variant. We also captured the virus-virus fusion events, which provided pieces of structural evidence for Delta's attenuated dependency on cellular factors for fusion activation, and proposed a model of S-mediated membrane fusion. Besides, site-specific glycan analysis revealed increased oligomannose-type glycosylation of native Delta S than that of the WT S. Together, these results disclose distinctive factors of Delta being the most virulent SARS-CoV-2 variant.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Fusión de Membrana , Glicosilación , Glicoproteína de la Espiga del Coronavirus
2.
Sci Adv ; 8(2): eabl8812, 2022 Jan 14.
Artículo en Inglés | MEDLINE | ID: covidwho-1642794

RESUMEN

To reduce the severe health risk and the huge economic impact associated with the fomite transmission of SARS-CoV-2, an imidazolium-based zwitterionic polymer was designed, synthesized, and demonstrated to achieve contact deactivation of a human coronavirus under dry ambient conditions that resemble fomite transmission. The zwitterionic polymer further demonstrated excellent antifouling properties, reducing the adhesion of coronavirus and the formation of bacteria biofilms under wetted conditions. The polymer was synthesized using a substrate-independent and solvent-free process, leveraging an all-dry technique named initiated chemical vapor deposition (iCVD). The broad applicability of this approach was demonstrated by applying the polymer to a range of substrates that are curved and/or with high-aspect-ratio nano/microporous structures, which remained intact after the coating process. The zwitterionic polymer and the synthesis approach reported here present an effective solution to mitigate viral transmission without the need for manual disinfection, reducing the health and economic impact of the ongoing pandemic.

3.
Cell ; 183(3): 730-738.e13, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: covidwho-746087

RESUMEN

SARS-CoV-2 is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins, the detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryoelectron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in pre- and postfusion conformations were determined to average resolutions of 8.7-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed overall processing states of the native glycans highly similar to that of the recombinant glycoprotein glycans. The native conformation of the ribonucleoproteins (RNPs) and their higher-order assemblies were revealed. Overall, these characterizations revealed the architecture of the SARS-CoV-2 virus in exceptional detail and shed light on how the virus packs its ∼30-kb-long single-segmented RNA in the ∼80-nm-diameter lumen.


Asunto(s)
Betacoronavirus/fisiología , Betacoronavirus/ultraestructura , Ensamble de Virus , Animales , Chlorocebus aethiops , Microscopía por Crioelectrón , Humanos , Espectrometría de Masas , Modelos Moleculares , Conformación Proteica , SARS-CoV-2 , Células Vero , Proteínas Virales/química , Proteínas Virales/ultraestructura , Cultivo de Virus
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