Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing : E1 group (BD55-3152, BD55-3546 BD5-5840) F3 (BD55-3372, BD55-4637 BD55-5514). Using approaches, examine determinants which potent can largely evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites critical functions along selective complementary targeting positively charged are important ACE2 binding. Together conserved epitopes, lead expanded neutralization breadth resilience shift associated viral results study demonstrate excellent qualitative agreement between predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

Exploring the pathogenic and transmission characteristics of JN.1 in golden hamsters based on different attack methods DOI
Ruixue Liu, Fang Song, Li Sun

et al.

Virology, Journal Year: 2025, Volume and Issue: 608, P. 110548 - 110548

Published: April 17, 2025

Language: Английский

Citations

0

Beyond COVID-19: the promise of next-generation coronavirus vaccines DOI Creative Commons

Reshma Koolaparambil Mukesh,

Claude Kwe Yinda, Vincent J. Munster

et al.

npj Viruses, Journal Year: 2024, Volume and Issue: 2(1)

Published: Aug. 22, 2024

Abstract Coronaviruses (CoVs) have caused three global outbreaks: severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) in 2003, Middle East (MERS-CoV) 2012, and SARS-CoV-2 2019, with significant mortality morbidity. The impact of disease 2019 (COVID-19) raised serious concerns about the preparedness for a pandemic. Furthermore, changing antigenic landscape led to new variants increased transmissibility immune evasion. Thus, development broad-spectrum vaccines against current future emerging CoVs will be an essential tool pandemic preparedness. Distinct phylogenetic features within complicate limit process generating pan-CoV vaccine capable targeting entire Coronaviridae family. In this review, we aim provide detailed overview CoVs, their phylogeny, various efforts developing vaccines, future.

Language: Английский

Citations

3

SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development DOI Creative Commons
Fabrizio Angius,

Silvia Puxeddu,

S Zaimi

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 17 - 17

Published: Dec. 28, 2024

The COVID-19 pandemic, driven by the rapid evolution of SARS-CoV-2 virus, presents ongoing challenges to global public health. is characterized rapidly evolving mutations, especially in (but not limited to) spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading multiple pandemic waves with over half a billion cases seven million deaths globally. Despite several strategies, from development administration design availability antivirals, including monoclonal antibodies, already having been employed, persistent circulation virus emergence new variants continue result high case numbers fatalities. In past four years, immense research efforts contributed much our understanding viral pathogenesis mechanism, syndrome, host-microbe interactions, effective vaccines, diagnostic tools, treatments. focus this review provide comprehensive analysis functional impact on diagnosis, treatments, effectiveness. We further discuss safety pregnancy implications hybrid immunity long-term protection against infection, as well latest developments pan-coronavirus nasal formulations, emphasizing need for continued surveillance, research, adaptive health strategies response race.

Language: Английский

Citations

3

Tracking KP.2 SARS-CoV-2 Variant in India and the Clinical Profile of KP.2 Cases in Maharashtra, India DOI Open Access
Rajesh Karyakarte, Rashmita Das, Varsha Potdar

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 3, 2024

Background: Following the emergence of JN.1 SARS-CoV-2 variant, variants with key mutations in spike protein, such as L455F, F456L, and R346T, were identified. In early January 2024, KP.2 (JN.1.11.1.2) variant was first identified clinical samples. Its increasing global prevalence has raised concerns over its transmission impact. The study investigates KP.2*'s (*indicates all sub-lineages) spread severity Maharashtra. Methods: This involved 5,173 Indian whole genome sequences collection dates between November 1, 2023 June 24, 2024. Lineage analysis performed using Nextclade software (version 3.8.0). Telephonic interviews conducted to confirm demographic details obtain information on KP.2* cases. obtained data recorded analyzed Microsoft® Excel (Microsoft Corporation, Redmond, WA). Results: Among analyzed, JN.1* appeared predominant lineage (65.96%, 3412/5173), followed by (7.83%, 405/5173) KP.1* (3.27%, 169/5173). India, detected December 2, 2023, Odisha. majority from Maharashtra (248/405, 61.23%), West Bengal (38/405, 9.38%), Gujarat (27/405, 6.67%), Rajasthan (24/405, 5.93%). reported included 160 cases Of these, 95.63% (153/160) presented mild symptoms, fever (108/160, 67.50%), cold (87/160, 54.38%), cough (80/160, 50%), sore throat (44/160, 27.5%), body ache (43/160, 26.88%), fatigue (42/160, 26.25%). About 33.13% (53/160) required institutional quarantine or hospitalization, rest managed at home. those hospitalized, 50.94% (27/53) received conservative treatment, while 49.06% (26/53) needed supplemental oxygen, steroids, antiviral therapy. Regarding vaccination status, 89.38% (143/160) had least one dose COVID-19 vaccine, whereas 10% (16/160) unvaccinated, unvaccinated being children aged zero nine years (7/16, 43.75%). overall recovery rate for 99.38% (159/160), only 0.62% (1/160) succumbing disease. Conclusion: become dominant India Despite affected individuals experiencing studies have shown lower neutralization titers high infectivity due FLiRT mutations, suggesting KP.2's potential rise dominance.

Language: Английский

Citations

2

Advancing CRISPR-Based Solutions for COVID-19 Diagnosis and Therapeutics DOI Creative Commons

Roaa Hadi,

Abhishek Poddar,

Shivakumar Sonnaila

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(21), P. 1794 - 1794

Published: Oct. 30, 2024

Since the onset of COVID-19 pandemic, a variety diagnostic approaches, including RT-qPCR, RAPID, and LFA, have been adopted, with RT-qPCR emerging as gold standard. However, significant challenge in diagnostics is wide range symptoms presented by patients, necessitating early accurate diagnosis for effective management. Although precise molecular technique, it not immune to false-negative results. In contrast, CRISPR-based detection methods SARS-CoV-2 offer several advantages: they are cost-effective, time-efficient, highly sensitive, specific, do require sophisticated instruments. These also show promise scalability, enabling tests. CRISPR technology can be customized target any genomic region interest, making versatile tool applications beyond diagnostics, therapeutic development. The CRISPR/Cas systems provide gene targeting immense potential creating next-generation therapeutics. One key advantages CRISPR/Cas-based therapeutics ability perform multiplexing, where different sgRNAs or crRNAs multiple sites within same gene, reducing likelihood viral escape mutants. Among various systems, CRISPR/Cas13 CARVER (Cas13-assisted restriction expression readout) particularly promising. broad single-stranded RNA viruses, them suitable treatment diseases, SARS-CoV-2. efficacy safety must thoroughly evaluated pre-clinical clinical settings. While biotechnologies yet fully harnessed control current there an optimism that limitations system overcome soon. This review discusses how strategies revolutionize disease development, better preparing us future threats.

Language: Английский

Citations

1

Predictive Assessment of the Antiviral Properties of Imperata cylindrica against SARS‐CoV‐2 DOI Creative Commons
Frank Eric Tatsing Foka, Hazel Tumelo Mufhandu

Advances in Virology, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

The omicron variant and its sublineages are highly contagious, they still constitute a global source of concern despite vaccinations. Hospitalizations mortality rates resulting from infections by these variants common. existing therapeutic alternatives have presented various setbacks such as low potency, poor pharmacokinetic profiles, drug resistance. need for alternative options cannot be overemphasized. Plants their phytochemicals present interesting characteristics that make them suitable candidates the development antiviral agents. This study aimed to investigate potential Imperata cylindrica ( I. ). Specifically, objective this was identify display inhibitory effects against SARS‐CoV‐2 main protease (M pro ), conserved protein among coronaviruses. Molecular docking in silico assays were used assess 72 phytocompounds found ligands M (6LU7) target. Only eight (bifendate, cylindrene, tabanone, siderin, 5‐hydroxy‐2‐[2‐(2‐hydroxyphenyl)ethyl]‐4H‐1‐benzopyran‐4‐one, maritimin, 5‐methoxyflavone, flavone) displayed high binding affinities with scores ranging −5.6 kcal/mol −9.1 kcal/mol. toxicological revealed tabanone best safest phytochemical an agent coronavirus protease. Thus, served baseline further vitro vivo assessment validate findings.

Language: Английский

Citations

0

SARS-CoV-2 and Environmental Changes: The Perfect Storm DOI Creative Commons
Mario Caldarelli, Pierluigi Rio, Vincenzo Giambra

et al.

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(11), P. 11835 - 11852

Published: Oct. 23, 2024

The COVID-19 pandemic has had a significant impact on the global economy. It also provided insights into how looming climate crisis might be addressed, as there are several similarities between challenges proposed by and those expected from coming emergency. is an immediate health threat, but change represents more gradual insidious risk that will lead to long-term consequences for human health. Research shows change, air pollution pandemics have negative Recent studies show mortality increases with extremes. goal of our review analyze clinical findings they affected while providing insight emergence new variants their ability evade immune system. We selected synthesized data primary studies, reviews, meta-analyses, systematic reviews. Selection was based rigorous methodological relevance criteria. Indeed, variant SARS-CoV-2, named JN.1, emerged dominant, first in United States then worldwide; specific mutations its spike proteins increase transmissibility. According World Health Organization (WHO), JN.1 currently most reported interest (VOI), having been identified 132 countries. highlight link pandemics, emphasizing need action, targeted medical approaches scientific innovation.

Language: Английский

Citations

0

Safety and Immunogenicity of Omicron Protein Vaccines in mRNA-Vaccinated Adolescents: A Phase 3, Randomised Trial DOI Creative Commons

Chijioke Bennett,

Gordon Chau,

Elizabeth Clayton

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

Summary Objectives Safety and immunogenicity assessment of updated monovalent bivalent SARS-CoV-2 vaccines in adolescents. Methods This phase 3, double-blinded study randomised 12–<18-year-old participants, who received ≥2 prior doses an approved/authorised mRNA-based COVID-19 vaccine, 1:1 to receive NVX-CoV2601 (XBB.1.5) or a vaccine (NVX-CoV2373 [Wuhan] + NVX-CoV2601). The primary endpoint was day-28 neutralizing antibody (nAb) geometric mean titres (GMTs) against XBB.1.5. endpoints were solicited reactogenicity ≤7 days unsolicited adverse events (AEs) ≤28 post vaccination frequency/severity predefined AEs special interest through day 180. Results Of 401 nAb GMTs XBB.1.5 increased (GMFR [95% CI]) for both (12.2 [9.5–15.5]) the (8.4 [6.8–10.3]); post-vaccination responses ancestral JN.1 variant also observed. Increases anti-spike IgG levels comparable between groups. Solicited mild moderate, with similar occurrence among Severe serious rare unrelated vaccines; no PIMMCs myocarditis/pericarditis reported. Conclusions elicited more robust virus, compared formulation. safety profile within each group consistent prototype (NVX-CoV2373).

Language: Английский

Citations

0

FLiRTing with danger: The emergence of the KP.2 Omicron variant DOI Creative Commons

Yashu,

Shiv Shankar Shukla, Honey Goel

et al.

Asian Pacific Journal of Tropical Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

As new COVID-19 strains surface and proliferate over the world, pandemic is still evolving[1]. The FLiRT variants are one such family of that have recently drawn notice. They a Omicron sub-variants quickly becoming dominant. These include KP.2 KP.1.1. Due to certain changes in virus's spike proteins, these been dubbed "FLiRT." nickname comes from initials F L, R T, which stand for important mutations enable them avoid immunisation[2]. spreading more rapidly worldwide comparison with other variants. per available data, sub-variant will become most prevalent disease many developed nations including United States, Kingdom South Korea[3]. variant entered India November 2023 has spread into states highest prevalence Maharashtra. genomic surveillance data compiled by Indian SARS-CoV-2 Consortium (INSACOG), than 250 sequences reported India. records last 60 days, an approximate 29% uploaded Global Initiative on Sharing All Influenza Data (GISAID) India[4]. result greater mutations, this considered infectious previous disease, increasing chances its rapid surge number cases. Additionally, their ability evade immunity raises risk breakthrough infections, could lead rise hospitalisations deaths[4]. variants, KP.1.1, characterized symptoms similar those earlier cough, fever, fatigue, body aches, headache, loss taste, sore throat, nausea, diarrhoea. differ slightly sub-variants; however, severity varies according underlying medical conditions individual's current immunological state[5]. Pneumonia, severe respiratory distress, organ failure possible outcomes extreme thought higher transmission rate be forms[6]. Infectious Disease Society America, there 1.22- fold increase relative effective reproduction (Re) compared JN.1 variant, suggesting This attributed novel enhance spreadability. Droplets can source transmission, dangerous everyone, especially compromised immune systems. existing vaccines found less efficient providing protection against KP.1.1 as it increased virulence through alterations proteins[7]. research done experts, vaccination does provide symptoms, helps preventing hospitalisation thus reduces morbidity or deaths caused but saying so newer questionable. Vaccination decreases decreasing viral load even if cannot shield individual disease[8]. predictions, believed show resistance towards vaccinations primarily XB2L.5 strain. To act newer/revised required lineage main target. not protect possibility catching infection would decrease associated. strain however discussion mutation level high exists escape host's defence triggered due vaccination[9]. Inculcating preventive measures our daily life best way impact variant. hot weather acts adjunct transmission. Measures like vaccination, staying at home sick, maintaining social distancing crowded places, wearing mask public places good personal hygiene help prevention disease[10,11]. Conflict interest statement authors declare no conflict interest. Funding received extramural funding study. Authors' contributions Y SS conceptualized designed work, carried out collection, drafted article. HG performed analysis interpretation. VC critically reviewed PAC article, responsible final approval version published. Publisher's note Publisher Journal remains neutral regard jurisdictional claims published maps institutional affiliations. Edited Zhang Q, Lei Y, Pan

Language: Английский

Citations

0

Quantitative Characterization and Prediction of the Binding Determinants and Immune Escape Hotspots for Groups of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling of the SARS-CoV-2 Spike Complexes with Antibodies DOI Open Access
Mohammed Alshahrani, Victoria N. Parikh, Brian Foley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The growing body of experimental and computational studies suggested that the cross-neutralization antibody activity against Omicron variants may be driven by balance tradeoff multiple energetic factors interaction contributions evolving escape hotspots involved in antigenic drift convergent evolution. However, dynamic details quantifying contribution these factors, particularly balancing nature specific interactions formed antibodies with epitope residues remain scarcely characterized. In this study, we performed molecular dynamics simulations, ensemble-based deep mutational scanning SARS-CoV-2 spike binding free energy computations for two distinct groups broadly neutralizing : E1 group (BD55-3152, BD55-3546 BD5-5840) F3 (BD55-3372, BD55-4637 BD55-5514). Using approaches, examine determinants which potent can largely evade immune resistance. Our analysis revealed emergence a small number positions correspond to R346 K444 strong van der Waals act synchronously leading large contribution. According our results, Abs effectively exploit hotspot clusters hydrophobic sites critical functions along selective complementary targeting positively charged are important ACE2 binding. Together conserved epitopes, lead expanded neutralization breadth resilience shift associated viral results study demonstrate excellent qualitative agreement between predicted mutations respect latest experiments on average scores. We argue epitopes leverage stability binding, while tend emerge synergistically electrostatic interactions.

Language: Английский

Citations

0