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

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 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.

Language: Английский

---

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

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 167 - 167

Published: Jan. 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.

Language: Английский

---

Molecular basis of receptor binding and antibody neutralization of Omicron

Nature, Journal Year: 2022, Volume and Issue: 604(7906), P. 546 - 552

Published: Feb. 28, 2022

Language: Английский

---

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

Science, Journal Year: 2022, Volume and Issue: 376(6591)

Published: March 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.

Language: Английский

---

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

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(7), P. 1008 - 1020

Published: June 27, 2022

Language: Английский

---

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

Cell, Journal Year: 2022, Volume and Issue: 185(16), P. 2952 - 2960.e10

Published: June 16, 2022

Language: Английский

---

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

Cell, Journal Year: 2022, Volume and Issue: 186(1), P. 112 - 130.e20

Published: Dec. 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.

Language: Английский

---

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

Cell Host & Microbe, Journal Year: 2022, Volume and Issue: 30(8), P. 1093 - 1102.e3

Published: April 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.

Language: Английский

---

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

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 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.

Language: Английский

---

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

MedComm, Journal Year: 2022, Volume and Issue: 3(1)

Published: March 1, 2022

Abstract New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread the virus in ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), latest variant concern (VOC), has so far shown exceptional and infectivity established itself as dominant recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for recognition binding to host cell angiotensin‐converting enzyme receptors. harbors cluster substitutions/deletions/insertions, more than 30 mutations are located spike. Some noticeable mutations, including K417N, T478K, N501Y, P681H, shared with previous VOCs Alpha, Beta, Gamma, or Delta have been proven be associated higher transmissibility, viral infectivity, immune evasion potential. Studies revealed that partially resistant neutralizing activity therapeutic antibodies convalescent sera, which poses significant challenges clinical effectiveness current vaccines antibodies. We provide comprehensive analysis summary epidemiology escape mechanisms variant. also suggest some strategies against This review, therefore, aims information further research efforts prevent contain impact new during

Language: Английский

---