Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike

Cell Reports, Год журнала: 2022, Номер 39(13), С. 111009 - 111009

Опубликована: Июнь 1, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences their pathobiology, here we determine cryoelectron microscopy (cryo-EM) structures of the S ectodomain and compare these with previously determined BA.1 structures. receptor-binding domain (RBD) mutations induce remodeling RBD structure, resulting tighter packing improved thermostability. Interprotomer interactions are enhanced closed (or 3-RBD-down) S, while fusion peptide is less accessible antibodies than Binding pseudovirus neutralization assays reveal extensive immune evasion defining epitopes two outer face-binding antibodies, DH1044 DH1193, that neutralize both BA.2. Taken together, our results indicate stabilization state through interprotomer RBD-RBD a hallmark variant show key functional regions proteins.

Язык: Английский

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Omicron variant (B.1.1.529) and its sublineages: What do we know so far amid the emergence of recombinant variants of SARS-CoV-2?

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 154, С. 113522 - 113522

Опубликована: Авг. 15, 2022

Since the start of COVID-19 pandemic, numerous variants SARS-CoV-2 have been reported worldwide. The advent concern (VOCs) raises severe concerns amid serious containment efforts against that include physical measures, pharmacological repurposing, immunization, and genomic/community surveillance. Omicron variant (B.1.1.529) has identified as a highly modified, contagious, crucial among five VOCs SARS-CoV-2. increased affinity spike protein (S-protein), host receptor, angiotensin converting enzyme-2 (ACE-2), due to higher number mutations in receptor-binding domain (RBD) S-protein proposed primary reason for decreased efficacy majorly available vaccines transmissible nature variant. Because its significant competitive advantage, sublineages swiftly surpassed other become dominant circulating lineages nations. prevalent strain United Kingdom South Africa. Furthermore, emergence recombinant through conjunction with or by mixing variant's sublineages/subvariants poses major threat humanity. This various issues hazards regarding sublineages, such an breakout susceptible populations fully vaccinated persons. As result, understanding features genetic implications this is crucial. Hence, we explained depth evolution analyzed repercussions on infectiousness, dissemination ability, viral entry mechanism, immune evasion. We also presented viewpoint feasible strategies precluding counteracting any future catastrophic spread omicron could result detrimental wave cases.

Язык: Английский

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SARS-CoV-2: Evolution and Emergence of New Viral Variants

Viruses, Год журнала: 2022, Номер 14(4), С. 653 - 653

Опубликована: Март 22, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent responsible for disease 2019 (COVID-19). high rate of mutation this virus associated with a quick emergence new viral variants that have been rapidly spreading worldwide. Several mutations documented in receptor-binding domain (RBD) spike protein increases interaction between SARS-CoV-2 and its cellular receptor, angiotensin-converting enzyme (ACE2). Mutations can increase spread rate, severity, ability to evade either immune protective responses, monoclonal antibody treatments, or efficacy current licensed vaccines. This review aimed highlight functional classification used by World Health Organization (WHO), Phylogenetic Assignment Named Global Outbreak (PANGO), Initiative on Sharing All Influenza Data (GISAID), Nextstrain, an open-source project harness scientific public health potential pathogen genome data, chronological concern (VOCs) interest (VOIs), major findings related spread, are involved evasion host responses elicited prior infections protection induced vaccination.

Язык: Английский

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SARS-CoV-2 spike L452R mutation increases Omicron variant fusogenicity and infectivity as well as host glycolysis

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Март 9, 2022

Язык: Английский

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Structural and biochemical mechanism for increased infectivity and immune evasion of Omicron BA.2 variant compared to BA.1 and their possible mouse origins

Cell Research, Год журнала: 2022, Номер 32(7), С. 609 - 620

Опубликована: Май 31, 2022

Abstract The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies show that the spike trimer exhibits 11-fold and 2-fold higher potency in to human ACE2 than from wildtype (WT) BA.1 strains. structure of complexed with reveals all three receptor-binding domains (RBDs) are open conformation, ready for binding, thus providing basis increased infectivity strain. JMB2002, therapeutic antibody was shown efficiently inhibit BA.1, also shows potent neutralization activities against BA.2. In addition, both trimers able bind mouse high potency. contrast, WT binds well cat but not ACE2. structures bound reveal their affinity interactions. Together, these results suggest possible evolution pathway variants via human-cat-mouse-human circle, which could have important implications establishing an effective strategy combating SARS-CoV-2 viral infections.

Язык: Английский

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