Predicting antibody and ACE2 affinity for SARS-CoV-2 BA.2.86 and JN.1 with in silico protein modeling and docking DOI Creative Commons
Shirish Yasa, Sayal Guirales-Medrano, Denis Jacob Machado

et al.

Frontiers in Virology, Journal Year: 2024, Volume and Issue: 4

Published: July 19, 2024

The emergence of SARS-CoV-2 lineages derived from Omicron, including BA.2.86 (nicknamed “Pirola”) and its relative, JN.1, has raised concerns about their potential impact on public personal health due to numerous novel mutations. Despite this, predicting implications based solely mutation counts proves challenging. Empirical evidence JN.1’s increased immune evasion capacity in relation previous variants is mixed. To improve predictions beyond what possible counts, we conducted extensive silico analyses the binding affinity between RBD different (Wuhan-Hu-1, BA.1/B.1.1.529, BA.2, XBB.1.5, BA.2.86, JN.1) neutralizing antibodies vaccinated or infected individuals, as well human angiotensin-converting enzyme 2 (ACE2) receptor. We observed no statistically significant difference JN.1 other variants. Therefore, conclude that new have pronounced escape infection compared However, minor reductions for both ACE2 were noted JN.1. Future research this area will benefit structural memory B-cell should emphasize importance choosing appropriate samples studies assess protection provided by vaccination infection. Moreover, fitness benefits genomic variation outside need be investigated. This contributes understanding variants’ health.

Language: Английский

Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread DOI

Dinah V. Parums

Medical Science Monitor, Journal Year: 2023, Volume and Issue: 29

Published: Jan. 26, 2023

In November 2021, the World Health Organization (WHO) first identified Omicron variant of SARS-CoV-2, B.1.1.529, as a concern (VOC). By early 2022, and its five lineages, BA.1, BA.2, BA.3, BA.4. BA.5, had become predominant cause COVID-19 in most countries. The XBB.1.5 subvariant is sublineage XBB variant, recombinant two BA.2 sublineages, with F486P mutation spike protein that increases infectivity due to increased binding affinity angiotensin-converting enzyme 2 (ACE2) receptor. On week ending 21 January 2023, caused 49.1% cases US. rapid rise prevalence this may be explained by immune escape previous infection or vaccines, mutations F486P, for ACE2 Also, current booster vaccines not provide adequate protection from subvariant, which has been named media 'Kraken' subvariant. This Editorial aims present status SARS-CoV-2 reasons for, implications of, global spread.

Language: Английский

Citations

86
From Alpha to Omicron: How Different Variants of Concern of the SARS-Coronavirus-2 Impacted the World DOI Creative Commons

Mickensone Andre,

Lee-Seng Lau,

Marissa D. Pokharel

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(9), P. 1267 - 1267

Published: Sept. 21, 2023

SARS-CoV-2, the virus that causes COVID-19, is prone to mutations and generation of genetic variants. Since its first outbreak in 2019, SARS-CoV-2 has continually evolved, resulting emergence several lineages variants concern (VOC) have gained more efficient transmission, severity, immune evasion properties. The World Health Organization given these names according letters Greek Alphabet, starting with Alpha (B.1.1.7) variant, which emerged 2020, followed by Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Omicron (B.1.1.529) This review explores variation among different VOCs how made a global impact on pandemic.

Language: Английский

Citations

54
The SARS-CoV-2 Omicron recombinant subvariants XBB, XBB.1, and XBB.1.5 are expanding rapidly with unique mutations, antibody evasion, and immune escape properties – an alarming global threat of a surge in COVID-19 cases again? DOI Creative Commons
Chiranjib Chakraborty, Manojit Bhattacharya, Hitesh Chopra

et al.

International Journal of Surgery, Journal Year: 2023, Volume and Issue: 109(4), P. 1041 - 1043

Published: March 14, 2023

Chakraborty, Chiranjib PhD; Bhattacharya, Manojit; Chopra, Hitesh Islam, Md. Aminul; Saikumar, G.; Dhama, Kuldeep MVSc.PhD Author Information

Language: Английский

Citations

34
Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants DOI Creative Commons
Yubin Liu, Ziyi Wang, Xinyu Zhuang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 17, 2023

A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into vaccine-induced after prime-boost at both polyclonal monoclonal levels. We characterized VDJ sequence 118 antibodies (mAbs) found that 20 neutralizing mAbs showed varied potency breadth against a range including XBB.1.5, BQ.1.1, BN.1. Bispecific (bsAbs) based on nonoverlapping exhibited enhanced most antibody-evasive strains, such as The passive transfer or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta Omicron BA.2 variant. neutralization mechanisms these were determined by structural characterization. Overall, broad spectrum potent distinct can be induced in individuals immunized BBIBP-CorV, suggesting application potential vaccines for preventing infection variants.

Language: Английский

Citations

31
Markov State Models and Perturbation-Based Approaches Reveal Distinct Dynamic Signatures and Hidden Allosteric Pockets in the Emerging SARS-Cov-2 Spike Omicron Variant Complexes with the Host Receptor: The Interplay of Dynamics and Convergent Evolution Modulates Allostery and Functional Mechanisms DOI
Sian Xiao, Mohammed Alshahrani,

Grace Gupta

et al.

Journal of Chemical Information and Modeling, Journal Year: 2023, Volume and Issue: 63(16), P. 5272 - 5296

Published: Aug. 7, 2023

The new generation of SARS-CoV-2 Omicron variants displayed a significant growth advantage and increased viral fitness by acquiring convergent mutations, suggesting that the immune pressure can promote evolution leading to sudden acceleration evolution. In current study, we combined structural modeling, microsecond molecular dynamics simulations, Markov state models characterize conformational landscapes identify specific dynamic signatures spike complexes with host receptor ACE2 for recently emerged highly transmissible XBB.1, XBB.1.5, BQ.1, BQ.1.1 variants. Microsecond simulations Markovian modeling provided detailed characterization functional states revealed thermodynamic stabilization XBB.1.5 subvariant, which be contrasted more BQ.1 subvariants. Despite considerable similarities, mutations induce unique distributions states. results suggested variant-specific changes mobility in interfacial loops receptor-binding domain protein fine-tuned through crosstalk between could provide an evolutionary path modulation escape. By combining atomistic analysis perturbation-based approaches, determined important complementary roles mutation sites as effectors receivers allosteric signaling involved plasticity regulation communications. This study also hidden pockets control distribution flexible adaptable regions.

Language: Английский

Citations

29
Evolution and implications of SARS-CoV-2 variants in the post-pandemic era DOI Creative Commons
Emery Manirambona, Olalekan John Okesanya, Noah Olabode Olaleke

et al.

Deleted Journal, Journal Year: 2024, Volume and Issue: 21(1)

Published: June 28, 2024

Abstract SARS-CoV-2, the cause of COVID-19 pandemic, has introduced a challenging era characterized by persistent emergence subvariants. Even after World Health Organization announced end virus continues to evolve, posing significant challenges public health responses. This comprehensive review examines multifaceted impacts these subvariants, emphasizing their significance across diverse dimensions. SARS-CoV-2 genetic variability, especially at spike protein region, which given rise Variants Concern, including Beta, Delta, Gamma, Alpha, and highly mutable Omicron, differently exhibit varying levels immune evasion, disease severity, transmissibility. Subvariants within Omicron lineage, BA.1, BA.2, BA.3, others, further complicate landscape with distinct signatures infectivity levels. The extend diagnostic techniques, treatment strategies, vaccine effectiveness, underscoring need for response preventive measures, genomic surveillance, vaccination campaigns. Sustaining interventions is critical, necessitating long-term strategies considering socio-political factors, community involvement, continuous adaptation healthcare approaches, robust monitoring, sustainable effectively combat virus's ever-changing landscape.

Language: Английский

Citations

10
Balancing Functional Tradeoffs between Protein Stability and ACE2 Binding in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic and Energetic Changes DOI Creative Commons
Gennady M. Verkhivker, Mohammed Alshahrani,

Grace Gupta

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(5), P. 1143 - 1143

Published: May 10, 2023

Evolutionary and functional studies suggested that the emergence of Omicron variants can be determined by multiple fitness trade-offs including immune escape, binding affinity for ACE2, conformational plasticity, protein stability allosteric modulation. In this study, we systematically characterize dynamics, structural affinities SARS-CoV-2 Spike complexes with host receptor ACE2 BA.2, BA.2.75, XBB.1 XBB.1.5 variants. We combined multiscale molecular simulations dynamic analysis interactions together ensemble-based mutational scanning residues network modeling epistatic interactions. This multifaceted computational study characterized mechanisms identified energetic hotspots mediate predicted increased enhanced BA.2.75 complexes. The results a mechanism driven spatially localized group centers, while allowing functionally beneficial neutral mutations in other interface positions. A network-based community model contributions is proposed revealing key role R498 Y501 mediating community-based couplings sites compensatory dynamics changes. also showed convergent evolutionary hotspot F486 modulate not only local but rewire global communities region F486P mutation to restore both variant which may explain growth advantages over variant. are consistent broad range rationalizing roles form coordinated enabling balance tradeoffs shaping up complex landscape virus transmissibility.

Language: Английский

Citations

22
A recombinant spike‐XBB.1.5 protein vaccine induces broad‐spectrum immune responses against XBB.1.5‐included Omicron variants of SARS‐CoV‐2 DOI Creative Commons
Cai He, Aqu Alu, Lei Hong

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: April 26, 2023

The XBB.1.5 subvariant has drawn great attention owing to its exceptionality in immune evasion and transmissibility. Therefore, it is essential develop a universally protective coronavirus disease 2019 vaccine against various strains of Omicron, especially XBB.1.5. In this study, we evaluated compared the responses induced by six different spike protein vaccines targeting ancestral or Omicron severe acute respiratory syndrome 2 (SARS-CoV-2) mice. We found that spike-wild-type immunization high titers neutralizing antibodies (NAbs) SARS-CoV-2. However, activity subvariants decreased sharply as number mutations receptor-binding domain (RBD) these viruses increased. Spike-BA.5, spike-BF.7, spike-BQ.1.1 strong NAbs BA.5, BF.7, BQ.1, BQ.1.1 but were poor protecting XBB XBB.1.5, which have more RBD mutations. sharp contrast, spike-XBB.1.5 vaccination can activate broadly other common Omicron. By performing correlation analysis, negatively correlated with subvariants. Vaccines effectively overcome resistance caused accumulation mutations, making most promising candidate universal variants.

Language: Английский

Citations

21
Emergence of COVID-19 Variants: An Update DOI Open Access
Parakriti Gupta, Varsha Gupta, Chander Mohan Singh

et al.

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: July 3, 2023

Severe acute respiratory disease virus-2 (SARS CoV-2) is one of the deadliest global threats faced by mankind to date. Despite colossal efforts, viral pandemic swept across all boundaries. Besides virulence and susceptible population, low proofreading capacity error-prone mechanism RNA-dependent RNA polymerase (RdRp) have contributed new variants reinfections. The World Health Organization has officially categorized these as concern or interest. This nomenclature not merely suffice surveillance but also effective treatment vaccine options in place. Coronavirus 2019 (COVID-19) propensity render available strategies futile owing mutations they acquire. futility can be attributed either ineffectiveness shortage supply given skyrocketing increase number cases. Presently, Omicron variant most widespread known escape protection, it immune-derived, vaccination-derived, hybrid. WHO recommended modification development policies few companies introduced Omicron-adapted jabs. Keeping view unending tale COVID-19 huge data on same, this review focuses providing insight into emergence ongoing dynamics variants.

Language: Английский

Citations

20
Ensemble-Based Mutational Profiling and Network Analysis of the SARS-CoV-2 Spike Omicron XBB Lineages for Interactions with the ACE2 Receptor and Antibodies: Cooperation of Binding Hotspots in Mediating Epistatic Couplings Underlies Binding Mechanism and Immune Escape DOI Open Access
Nishank Raisinghani, Mohammed Alshahrani,

Grace Gupta

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4281 - 4281

Published: April 12, 2024

In this study, we performed a computational study of binding mechanisms for the SARS-CoV-2 spike Omicron XBB lineages with host cell receptor ACE2 and panel diverse class one antibodies. The central objective investigation was to examine molecular factors underlying epistatic couplings among convergent evolution hotspots that enable optimal balancing antibody evasion variants BA.1, BA2, BA.3, BA.4/BA.5, BQ.1.1, XBB.1, XBB.1.5, XBB.1.5 + L455F/F456L. By combining evolutionary analysis, dynamics simulations, ensemble-based mutational scanning protein residues in complexes ACE2, identified structural stability affinity are consistent results biochemical studies. agreement deep experiments, our quantitative analysis correctly reproduced strong variant-specific effects BA.2 variants. It shown Y453W F456L mutations can enhance when coupled Q493 while these become destabilized R493 position variant. provided rationale mechanism variants, showing role Q493/R493 hotspot modulating between sites L455F lineages. receptors antibodies provide experimental evidence interactions physically proximal Y501, R498, Q493, L455F, determine binding, F486P instrumental mediating broad resistance. supports which impact on is mediated through small group universal hotspots, effect immune could be more variant-dependent modulated by conformationally adaptable regions.

Language: Английский

Citations

6