SARS-CoV-2 Omicron variant: recent progress and future perspectives

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

Опубликована: Апрель 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

Язык: Английский

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A Detailed Overview of SARS-CoV-2 Omicron: Its Sub-Variants, Mutations and Pathophysiology, Clinical Characteristics, Immunological Landscape, Immune Escape, and Therapies

Viruses, Год журнала: 2023, Номер 15(1), С. 167 - 167

Опубликована: Янв. 5, 2023

The COVID-19 pandemic has created significant concern for everyone. Recent data from many worldwide reports suggest that most infections are caused by the Omicron variant and its sub-lineages, dominating all previously emerged variants. numerous mutations in Omicron’s viral genome sub-lineages attribute it a larger amount of fitness, owing to alteration transmission pathophysiology virus. With rapid change structure, sub-variants, namely BA.1, BA.2, BA.3, BA.4, BA.5, dominate community with an ability escape neutralization efficiency induced prior vaccination or infections. Similarly, several recombinant sub-variants Omicron, XBB, XBD, XBF, etc., have emerged, which better understanding. This review mainly entails changes due having higher number mutations. binding affinity, cellular entry, disease severity, infection rates, importantly, immune evading potential them discussed this review. A comparative analysis Delta other variants evolved before gives readers in-depth understanding landscape infection. Furthermore, discusses range abilities possessed approved antiviral therapeutic molecules neutralizing antibodies functional against sub-variants. evolution is causing infections, but broader aspect their not been explored. Thus, scientific should adopt elucidative approach obtain clear idea about recently including variants, so effective vaccines drugs can be achieved. This, turn, will lead drop cases and, finally, end pandemic.

Язык: Английский

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Molecular basis of receptor binding and antibody neutralization of Omicron

Nature, Год журнала: 2022, Номер 604(7906), С. 546 - 552

Опубликована: Фев. 28, 2022

Язык: Английский

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Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529

Science, Год журнала: 2022, Номер 376(6591)

Опубликована: Март 24, 2022

The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (Omicron) variant and its resistance to neutralization by vaccinee convalescent sera are driving a search for monoclonal antibodies with potent neutralization. To provide insight into effective neutralization, we determined cryo-electron microscopy structures evaluated receptor binding domain (RBD) their ability bind neutralize B.1.1.529. Mutations altered 16% RBD surface, clustered on an ridge overlapping angiotensin-converting enzyme (ACE2)-binding surface reduced most antibodies. Substantial inhibitory activity was retained select antibodies-including A23-58.1, B1-182.1, COV2-2196, S2E12, A19-46.1, S309, LY-CoV1404-that accommodated these changes neutralized We identified combinations synergistic analysis revealed structural mechanisms maintenance against emerging variants.

Язык: Английский

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The humoral response and antibodies against SARS-CoV-2 infection

Nature Immunology, Год журнала: 2022, Номер 23(7), С. 1008 - 1020

Опубликована: Июнь 27, 2022

Язык: Английский

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Structural basis of human ACE2 higher binding affinity to currently circulating Omicron SARS-CoV-2 sub-variants BA.2 and BA.1.1

Cell, Год журнала: 2022, Номер 185(16), С. 2952 - 2960.e10

Опубликована: Июнь 16, 2022

Язык: Английский

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SARS-CoV-2 replication in airway epithelia requires motile cilia and microvillar reprogramming

Cell, Год журнала: 2022, Номер 186(1), С. 112 - 130.e20

Опубликована: Дек. 2, 2022

How SARS-CoV-2 penetrates the airway barrier of mucus and periciliary mucins to infect nasal epithelium remains unclear. Using primary epithelial organoid cultures, we found that virus attaches motile cilia via ACE2 receptor. traverses layer, using as tracks access cell body. Depleting blocks infection for other respiratory viruses. progeny attach microvilli 24 h post-infection trigger formation apically extended highly branched organize viral egress from back into supporting a model dispersion throughout tissue mucociliary transport. Phosphoproteomics kinase inhibition reveal microvillar remodeling is regulated by p21-activated kinases (PAK). Importantly, Omicron variants bind with higher affinity show accelerated entry. Our work suggests cilia, microvilli, mucociliary-dependent flow are critical efficient replication in epithelia.

Язык: Английский

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Neutralization of SARS-CoV-2 Omicron sub-lineages BA.1, BA.1.1, and BA.2

Cell Host & Microbe, Год журнала: 2022, Номер 30(8), С. 1093 - 1102.e3

Опубликована: Апрель 25, 2022

Recent reports of SARS-CoV-2 Omicron variant sub-lineages, BA.1, BA.1.1, and BA.2, have reignited concern over potential escape from vaccine- infection-induced immunity. We examine the sensitivity these sub-lineages other major variants to neutralizing antibodies mRNA-vaccinated boosted individuals, as well recovered COVID-19 patients, including those infected with Omicron. find that all especially BA.1 exhibit substantial immune is largely overcome by mRNA vaccine booster doses. While BA.1.1 escapes almost completely neutralization early-pandemic patient sera a lesser extent Delta-infected sensitive Omicron-infected sera. Critically, are comparably neutralized These results highlight importance doses for protection against provide insight into immunity natural infection sub-lineages.

Язык: Английский

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Omicron SARS-CoV-2 mutations stabilize spike up-RBD conformation and lead to a non-RBM-binding monoclonal antibody escape

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 24, 2022

Omicron SARS-CoV-2 is rapidly spreading worldwide. To delineate the impact of emerging mutations on spike's properties, we performed systematic structural analyses apo spike and its complexes with human ACE2 or S309 neutralizing antibody (NAb) by cryo-EM. The preferentially adopts one-RBD-up conformation both before after binding, which in sharp contrast to orchestrated conformational changes create more up-RBDs upon binding as observed prototype other four variants concern (VOCs). Furthermore, found that S371L, S373P S375F substitutions enhance stability prevent exposing triggered binding. increased restricts accessibility S304 NAb, targets a cryptic epitope closed conformation, thus facilitating immune evasion Omicron. These results expand our understanding receptor mechanism.

Язык: Английский

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The rapid rise of SARS‐CoV‐2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants

MedComm, Год журнала: 2023, Номер 4(2)

Опубликована: Март 15, 2023

As the fifth variant of concern SARS-CoV-2 virus, Omicron (B.1.1.529) has quickly become dominant type among previous circulating variants worldwide. During wave, several subvariants have emerged, with some exhibiting greater infectivity and immune evasion, accounting for their fast spread across many countries. Recently, two subvariants, BQ.1 XBB lineages, including BQ.1.1, XBB.1, XBB.1.5, a global public health issue given ability to escape from therapeutic monoclonal antibodies herd immunity induced by prior coronavirus disease 2019 (COVID-19) vaccines, boosters, infection. In this respect, which been established harbor rare mutation F486P, demonstrates superior transmissibility compared other emerged as strain in This review provides comprehensive overview epidemiological features, spike mutations, evasion lineages. We expounded on mechanisms underlying mutations neutralizing vaccinated or convalescent COVID-19 individuals (mAbs) proposed strategies prevention against sublineages.

Язык: Английский

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