Emerging Variants of SARS-CoV-2

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Coronaviruses".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 5254

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Guest Editor
State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Institute of Infectious Disease and Biosecurity, School of Life Sciences, Fudan University, Shanghai 200433, China
Interests: coronavirus; HIV-1; antibody; vaccine
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Special Issue Information

Dear Colleagues,

The SARS-CoV-2 virus has undergone substantial evolution, leading to new variants such as JN.1 and KP.2, among others. These new variants continue to shape the trajectory of the COVID-19 pandemic, underscoring the need for continuous monitoring and adaptive response strategies to effectively address their challenges. These variants can significantly impact transmission, disease severity, and immune evasion, necessitating ongoing research to understand and mitigate their effects.

Last year, we successfully organized the Special Issue "Recombinant Variants of SARS-CoV-2," which published six papers. In this reopened Special Issue, "Emerging Variants of SARS-CoV-2," we invite original research articles and reviews exploring the dynamics and implications of newly emerging variants. This includes, but is not limited to:

  • The evolution and epidemiology of emerging SARS-CoV-2 variants.
  • Real-time assessment of the risk posed by new variants.
  • Virological characteristics of emerging variants, including transmissibility, immune evasion, ACE2 binding affinity, infectivity, fusogenicity, structural information, and pathogenicity in animal models.
  • Development and efficacy of vaccines, antibodies, and drugs against new SARS-CoV-2 variants.

Your contributions will be instrumental in advancing our understanding of these emerging threats and informing public health strategies. I look forward to your valuable submissions.

Dr. Pengfei Wang
Guest Editor

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Keywords

  • SARS-CoV-2
  • variants
  • evolution and epidemiology
  • immune evasion
  • ACE2
  • structure
  • vaccines
  • antibodies
  • drugs

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Published Papers (3 papers)

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14 pages, 2135 KiB  
Article
The Association Between the Ct Value of SARS-CoV-2 and the Risk of Death from COVID-19 in Amazonas, Peru, During the Circulation of the Lambda, Gamma, and Delta Variants
by Christian J. Campos, Stella M. Chenet, Cecilia Montes-Jave and Fiorella Krapp
Viruses 2025, 17(4), 558; https://doi.org/10.3390/v17040558 - 12 Apr 2025
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Abstract
This study aimed to assess the association between the cycle threshold (Ct) values of SARS-CoV-2 and the risk of death from COVID-19 in adult patients from the Amazonas region of Peru during the circulation of the Lambda, Gamma, and Delta variants. The study [...] Read more.
This study aimed to assess the association between the cycle threshold (Ct) values of SARS-CoV-2 and the risk of death from COVID-19 in adult patients from the Amazonas region of Peru during the circulation of the Lambda, Gamma, and Delta variants. The study population included both hospitalized and outpatient patients, symptomatic and asymptomatic, between August 2020 and August 2021. The standardized Ct values of the ORF1ab gene were categorized into low and high Ct groups based on the median Ct value (28.4). Mortality data within 60 days were obtained from the Peruvian epidemiological surveillance system (Notiweb). The risk of death was estimated using Cox regression, adjusting for relevant predictors and potential confounding variables. Among symptomatic COVID-19 patients, no significant difference in the risk of death was observed between those with low and high Ct values (adjusted hazard ratio [aHR] = 1.61; 95% confidence interval [CI], 0.97–2.67; p = 0.067). However, hospitalized patients with low Ct values had a significantly higher risk of death compared to those with high Ct values (aHR = 1.82; 95% CI, 1.06–3.12; p = 0.030). This association persisted after adjusting for age, sex, occupational group, symptom duration, comorbidities, and epidemic dynamics. In conclusion, while Ct values in symptomatic COVID-19 patients (both hospitalized and outpatient) are not associated with a 60-day mortality risk, a low Ct value is linked to an increased risk of death in hospitalized patients. Full article
(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)
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37 pages, 6270 KiB  
Article
AlphaFold2 Modeling and Molecular Dynamics Simulations of the Conformational Ensembles for the SARS-CoV-2 Spike Omicron JN.1, KP.2 and KP.3 Variants: Mutational Profiling of Binding Energetics Reveals Epistatic Drivers of the ACE2 Affinity and Escape Hotspots of Antibody Resistance
by Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta and Gennady Verkhivker
Viruses 2024, 16(9), 1458; https://doi.org/10.3390/v16091458 - 13 Sep 2024
Cited by 9 | Viewed by 3094
Abstract
The most recent wave of SARS-CoV-2 Omicron variants descending from BA.2 and BA.2.86 exhibited improved viral growth and fitness due to convergent evolution of functional hotspots. These hotspots operate in tandem to optimize both receptor binding for effective infection and immune evasion efficiency, [...] Read more.
The most recent wave of SARS-CoV-2 Omicron variants descending from BA.2 and BA.2.86 exhibited improved viral growth and fitness due to convergent evolution of functional hotspots. These hotspots operate in tandem to optimize both receptor binding for effective infection and immune evasion efficiency, thereby maintaining overall viral fitness. The lack of molecular details on structure, dynamics and binding energetics of the latest FLiRT and FLuQE variants with the ACE2 receptor and antibodies provides a considerable challenge that is explored in this study. We combined AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore ACE2-binding affinity while conferring beneficial immune escape. To examine immune escape mechanisms, we performed structure-based mutational profiling of the spike protein binding with several classes of antibodies that displayed impaired neutralization against BA.2.86, JN.1, KP.2 and KP.3. The results confirmed the experimental data that JN.1, KP.2 and KP.3 harboring the L455S and F456L mutations can significantly impair the neutralizing activity of class 1 monoclonal antibodies, while the epistatic effects mediated by F456L can facilitate the subsequent convergence of Q493E changes to rescue ACE2 binding. Structural and energetic analysis provided a rationale to the experimental results showing that BD55-5840 and BD55-5514 antibodies that bind to different binding epitopes can retain neutralizing efficacy against all examined variants BA.2.86, JN.1, KP.2 and KP.3. The results support the notion that evolution of Omicron variants may favor emergence of lineages with beneficial combinations of mutations involving mediators of epistatic couplings that control balance of high ACE2 affinity and immune evasion. Full article
(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)
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11 pages, 1157 KiB  
Brief Report
Remdesivir and Obeldesivir Retain Potent Antiviral Activity Against SARS-CoV-2 Omicron Variants
by Lauren Rodriguez, J. Lizbeth Reyes Zamora, Dong Han, Jasmine Moshiri, Nadine Peinovich, Clarissa Martinez, Pui Yan Ho, Jiani Li, Thomas Aeschbacher, Ross Martin, Andrew Pekosz, John P. Bilello, Jason K. Perry and Charlotte Hedskog
Viruses 2025, 17(2), 168; https://doi.org/10.3390/v17020168 - 25 Jan 2025
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Abstract
As new SARS-CoV-2 variants continue to emerge, it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA [...] Read more.
As new SARS-CoV-2 variants continue to emerge, it is important to evaluate the potency of antiviral drugs to support their continued use. Remdesivir (RDV; VEKLURY®) an approved antiviral treatment for COVID-19, and obeldesivir (ODV) are inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase Nsp12. Here we show these two compounds retain antiviral activity against the Omicron variants BA.2.86, BF.7, BQ.1, CH.1.1, EG.1.2, EG.5.1, EG.5.1.4, FL.22, HK.3, HV.1, JN.1, JN.1.7, JN.1.18, KP.2, KP.3, LB.1, XBB.1.5, XBB.1.5.72, XBB.1.16, XBB.2.3.2, XBC.1.6, and XBF when compared with reference strains. Genomic analysis identified 29 Nsp12 polymorphisms in these and previous Omicron variants. Phenotypic analysis of these polymorphisms confirmed no impact on the antiviral activity of RDV or ODV and suggests Omicron variants containing these Nsp12 polymorphisms remain susceptible to both compounds. These data support the continued use of RDV in the context of circulating SARS-CoV-2 variants and the development of ODV as an antiviral therapeutic. Full article
(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)
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