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Viruses
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Emerging Variants of SARS-CoV-2
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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 7852

Special Issue Editor

Dr. Pengfei Wang

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Published Papers (5 papers)

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16 pages, 2095 KiB  
Article
Identification of Clinical and Genomic Features Associated with SARS-CoV-2 Reinfections
by Francisco Muñoz-López, Antoni E. Bordoy, Francesc Català-Moll, Verónica Saludes, David Panisello Yagüe, Mariona Parera, Ignacio Blanco, Pere-Joan Cardona, Cristina Casañ, Ana Blanco-Suárez, Sandra Franco, Álvaro F. García-Jiménez, Roger Paredes, Bonaventura Clotet, Lourdes Mateu, Marc Noguera-Julian, Elisa Martró, José Ramón Santos and Marta Massanella
Viruses 2025, 17(6), 840; https://doi.org/10.3390/v17060840 - 11 Jun 2025
Viewed by 834
Abstract
Although SARS-CoV-2 reinfections remain a concern for healthcare systems worldwide, the factors driving them are still not fully understood. In this study, we examined data for 3303 individuals who experienced two SARS-CoV-2 infections between March 2020 and May 2022 from both clinical and [...] Read more.
Although SARS-CoV-2 reinfections remain a concern for healthcare systems worldwide, the factors driving them are still not fully understood. In this study, we examined data for 3303 individuals who experienced two SARS-CoV-2 infections between March 2020 and May 2022 from both clinical and viral genomics perspectives. Our findings indicate that viral evolution was the primary driver of reinfection. However, chronic conditions were common among reinfected individuals, including those under 26 years old, suggesting that the presence of underlying and/or chronic conditions increases susceptibility to reinfection. The median time elapsed between infections was one year, often coinciding with the emergence of new variants. While vaccination showed only a limited protective effect against reinfection, it drastically decreased the hospitalization rate, underscoring its role in mitigating disease severity. Our findings point to the need for more flexible vaccination strategies, especially for individuals with chronic conditions. Understanding the interactions between host factors and viral evolution is critical to strengthening prevention strategies and reducing the burden of reinfections and their possible long-term complications. Full article
(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)
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13 pages, 2137 KiB  
Article
Behavioral Dynamics, Genomic Insights, and Social Drivers of SARS-CoV-2 Waves and Variants in Cali, Colombia (2020–2023)
by Diana López-Alvarez, Nelson Rivera-Franco, Erica Aristizabal, Melissa Solarte, Andrés Castillo, Carlos A. Pardo and Beatriz Parra
Viruses 2025, 17(6), 800; https://doi.org/10.3390/v17060800 - 30 May 2025
Viewed by 465
Abstract
In Cali, Colombia, 405,689 COVID-19 cases were reported until March 2023, with 2463 complete genome sequences available for analysis. SARS-CoV-2 genomic data from Cali were analyzed to determine the prevalence of variants as well as the mutation frequencies. This study identified Nextstrain clades, [...] Read more.
In Cali, Colombia, 405,689 COVID-19 cases were reported until March 2023, with 2463 complete genome sequences available for analysis. SARS-CoV-2 genomic data from Cali were analyzed to determine the prevalence of variants as well as the mutation frequencies. This study identified Nextstrain clades, Pango lineages, and specific mutations in key viral proteins. A total of 23 Nextstrain clades and 118 Pango lineages were detected, including variants of interest (Lambda, Mu) and variants of concern (Alpha, Gamma, Delta, Omicron). Analysis identified 2424 missense mutations, with notable frequencies in NSP3 (465), S (367), NSP2 (205), N (180), ORF3a (144), NSP12b (113), and NSP13 (108). The study also observed a high prevalence of simultaneous transmission of multiple variants. The COVID-19 epidemic waves in Cali were shaped more by social and economic dynamics than by the emergence of specific SARS-CoV-2 variants. These findings highlight the importance of context-specific public health interventions to mitigate future outbreaks effectively. Full article
(This article belongs to the Special Issue Emerging Variants of SARS-CoV-2)
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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
Viewed by 489
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 13 | Viewed by 3737
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
Viewed by 1396
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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