Insight into SARS-CoV-2 Omicron variant immune escape possibility and variant independent potential therapeutic opportunities DOI Creative Commons
Mohammad Shah Alam

Heliyon, Journal Year: 2023, Volume and Issue: 9(2), P. e13285 - e13285

Published: Jan. 31, 2023

The Omicron, the latest variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in November 2021 Botswana, South Africa. Compared to other variants SARS-CoV-2, Omicron is most highly mutated, with 50 mutations throughout genome, which are spike (S) protein. These may help evade host immunity against vaccine. Epidemiological studies suggest that infectious and spreads rapidly, but causes significantly less disease than wild‐type strain SARS-CoV-2. With increased transmissibility a higher rate re-infection, has now become dominant worldwide predicted be able vaccine-induced immunity. Several clinical using plasma samples from individuals receiving two doses US Food Drugs Administration (FDA)-approved COVID-19 vaccines have shown reduced humoral immune response infection, T cell-mediated well preserved. In fact, protects disease, thus caused by remains mild. this review, I surveyed current status mechanisms context escape vaccines. also discuss potential implications therapeutic opportunities independent SARS-CoV-2 variants, including Omicron. A better understanding responses variant-independent interventions include potent antiviral, antioxidant, anti-cytokine activities pave way reducing Omicron-related complications, severity, mortality. Collectively, these insights point research gaps will aid development new-generation antiviral drugs combat its sublineages, or upcoming new

Language: Английский

Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic DOI Creative Commons
Wilhelm Furnon, Vanessa M. Cowton, Giuditta De Lorenzo

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging comprehensively compare many spikes that emerged during pandemic a single experimental platform. Here we generated panel recombinant viruses carrying different proteins from 27 circulating between 2020 and 2024 same genomic background. We then assessed several phenotypic traits both vitro vivo. found distinct among before after emergence Omicron variants. Spike post-Omicron maintained enhanced tropism for nasal epithelium large airways but displayed, over time, typical pre-Omicron Hence, with features pre- may continue emerge future.

Language: Английский

Citations

2
SARS-CoV-2 Evolution: On the Sudden Appearance of the Omicron Variant DOI Creative Commons
Ben Berkhout, Elena Herrera-Carrillo

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(7)

Published: March 16, 2022

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads rapidly and harbors many mutations in the spike protein, but origin this virus remains unclear. We address role unusual evolution mechanisms such as hypermutation, out-of-frame reading, recombination. Rather, regular Darwinian evolution, that is, repeated selection beneficial mutations, seems to have led appearance grossly altered protein variant.

Language: Английский

Citations

55
Omicron Spike Protein Has a Positive Electrostatic Surface That Promotes ACE2 Recognition and Antibody Escape DOI Creative Commons
Hin Hark Gan, John Zinno, Fabio Piano

et al.

Frontiers in Virology, Journal Year: 2022, Volume and Issue: 2

Published: June 10, 2022

High transmissibility is a hallmark of the Omicron variant SARS-CoV-2. Understanding molecular determinants Omicron’s will impact development intervention strategies. Here we map electrostatic potential surface Spike protein to show that major SARS-CoV-2 variants have accumulated positive charges in solvent-exposed regions protein, especially its ACE2-binding interface. Significantly, Spike-ACE2 complex has complementary surfaces. In contrast, interfaces between and neutralizing antibodies tend similar positively charged Structural modeling demonstrates property receptor binding domain (S RBD) plays role enhancing ACE2 recognition destabilizing Spike-antibody complexes. Specifically, S RBD favorable interaction energy with 3-5 times greater than Delta over range 20 Å, implying efficient host receptors. Computed affinities six representative RBD-antibody complexes can escape most targeting region RBD. Interestingly, straightforward assessment surfaces 18 correctly predicted status 80% cases. Collectively, our structural analysis implies been optimized simultaneously promote access human receptors evade antibodies. These findings suggest interactions are contributing factor for increased relative other variants.

Language: Английский

Citations

54
Contributions of adaptation and purifying selection to SARS-CoV-2 evolution DOI
Richard A. Neher

Virus Evolution, Journal Year: 2022, Volume and Issue: 8(2)

Published: July 1, 2022

Abstract Continued evolution and adaptation of SARS-CoV-2 has led to more transmissible immune-evasive variants with profound impacts on the course pandemic. Here I analyze virus over 2.5 years since its emergence estimate rates for synonymous non-synonymous changes separately within clades—well-defined monophyletic groups gradual evolution—and pandemic overall. The rate mutation is found be around 6 per year. Synonymous vary little from variant are compatible overall 7 year (or $7.5 \times 10^{-4}$ codon). In contrast, at which accumulate amino acid (non-synonymous mutations) was initially 12-16 year, but in 2021 2022 it dropped 6-9 evolution, that across variants, estimated about 26 $2.7 10^{-3}$ This strong acceleration compared clade indicates evolutionary process gave rise different qualitatively typical transmission chains likely dominated by adaptive evolution. further quantify spectrum mutations purifying selection proteins show massive global sampling sufficient site-specific fitness costs entire genome. Many accessory evolve under limited constraints short-term selection. About half other strongly deleterious.

Language: Английский

Citations

54
The SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant DOI

Izumi Kimura,

Daichi Yamasoba,

Hesham Nasser

et al.

iScience, Journal Year: 2022, Volume and Issue: 25(12), P. 105720 - 105720

Published: Dec. 1, 2022

Language: Английский

Citations

48
Comparative Analysis of SARS-CoV-2 Variants of Concern, Including Omicron, Highlights Their Common and Distinctive Amino Acid Substitution Patterns, Especially at the Spike ORF DOI Creative Commons
Marios Nikolaidis, Athanasios Papakyriakou, Katerina Chlichlia

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(4), P. 707 - 707

Published: March 29, 2022

In order to gain a deeper understanding of the recently emerged and highly divergent Omicron variant concern (VoC), study amino acid substitution (AAS) patterns was performed compared with those other four successful variants (Alpha, Beta, Gamma, Delta) one closely related interest (VoI-Lambda). The Spike ORF consistently emerges as an AAS hotspot in all six lineages, but this enrichment is significantly higher. progenitors each these VoC/VoI lineages underwent positive selection ORF. However, once they were established, their ORFs have been undergoing purifying selection, despite application global vaccination schemes from 2021 onwards. Our analyses reject hypothesis that heavily mutated receptor binding domain (RBD) introduced via recombination another Sarbecovirus. Thus, successive point mutations appear most parsimonious scenario. Intriguingly, we observed significant number wherein new residue not present at any homologous site among known Sarbecoviruses. Such should be further investigated potential adaptations human host. By studying phylogenetic distribution shared between (BA.1) lineage had highest (8/10) recurrent mutations.

Language: Английский

Citations

40
Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses DOI Creative Commons
Alexander G. Lucaci, Jordan D. Zehr, David Enard

et al.

Molecular Biology and Evolution, Journal Year: 2023, Volume and Issue: 40(7)

Published: July 1, 2023

Abstract Inference and interpretation of evolutionary processes, in particular the types targets natural selection affecting coding sequences, are critically influenced by assumptions built into statistical models tests. If certain aspects substitution process (even when they not direct interest) presumed absent or modeled with too crude a simplification, estimates key model parameters can become biased, often systematically, lead to poor performance. Previous work established that failing accommodate multinucleotide (or multihit, MH) substitutions strongly biases dN/dS-based inference towards false-positive inferences diversifying episodic selection, as does variation rate synonymous (SRV) among sites. Here, we develop an integrated analytical framework software tools simultaneously incorporate these sources complexity analyses. We found both MH SRV ubiquitous empirical alignments, incorporating them has strong effect on whether positive is detected (1.4-fold reduction) distributions inferred rates. With simulation studies, show this attributable reduced power caused using more complex model. After detailed examination 21 benchmark alignments new high-resolution analysis showing which parts alignment provide support for occurring along shorter branches tree explain significant fraction discrepant results detection. Our add growing body literature examines decades-old modeling (including finds be problematic comparative genomic data analysis. Because have impact detection even at level entire gene, recommend analyses type consider their inclusion matter routine. To facilitate procedure, developed, implemented, benchmarked simple well-performing testing able screen two biologically important confounding processes: site-to-site variation, instantaneous substitutions.

Language: Английский

Citations

25
Exploring and Learning the Universe of Protein Allostery Using Artificial Intelligence Augmented Biophysical and Computational Approaches DOI

Steve Agajanian,

Mohammed Alshahrani, Fang Bai

et al.

Journal of Chemical Information and Modeling, Journal Year: 2023, Volume and Issue: 63(5), P. 1413 - 1428

Published: Feb. 24, 2023

Allosteric mechanisms are commonly employed regulatory tools used by proteins to orchestrate complex biochemical processes and control communications in cells. The quantitative understanding characterization of allosteric molecular events among major challenges modern biology require integration innovative computational experimental approaches obtain atomistic-level knowledge the states, interactions, dynamic conformational landscapes. growing body studies empowered emerging artificial intelligence (AI) technologies has opened up new paradigms for exploring learning universe protein allostery from first principles. In this review we analyze recent developments high-throughput deep mutational scanning functions; applications latest adaptations Alpha-fold structural prediction methods dynamics allostery; frontiers integrating machine enhanced sampling techniques advances systems. We also highlight SARS-CoV-2 spike (S) revealing an important often hidden role regulation driving functional changes, binding interactions with host receptor, escape S which critical viral infection. conclude a summary outlook future directions suggesting that AI-augmented biophysical computer simulation beginning transform toward systematic landscapes, may bring about revolution drug discovery.

Language: Английский

Citations

23
Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations DOI Creative Commons
Lily E. Cohen, David Spiro, Cécile Viboud

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(6), P. e1010591 - e1010591

Published: June 30, 2022

In this review, we discuss the epidemiological dynamics of different viral infections to project how transition from a pandemic endemic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) might take shape. Drawing theories disease invasion and transmission dynamics, waning immunity in face evolution antigenic drift, empirical data influenza, dengue, seasonal coronaviruses, putative periodicity, severity, age SARS-CoV-2 as it becomes endemic. We review recent studies on epidemiology, immunology, that are particularly useful projecting endemicity highlight gaps warrant further research.

Language: Английский

Citations

33
Intrinsic furin-mediated cleavability of the spike S1/S2 site from SARS-CoV-2 variant B.1.1.529 (Omicron) DOI Creative Commons
Bailey Lubinski, Javier A. Jaimes, Gary R. Whittaker

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: April 22, 2022

The ability of SARS-CoV-2 to be primed for viral entry by the host cell protease furin has become one most investigated numerous transmission and pathogenicity features virus. variant B.1.1.529 (Omicron) emerged in late 2020 continued evolve is now present several distinct sub-variants. Here, we analyzed "furin cleavage site" spike protein (Omicron variant)

Language: Английский

Citations

30