Recombinant Variants of SARS-CoV-2

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "SARS-CoV-2 and COVID-19".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 7039

Special Issue Editor


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Guest Editor
Sch Life Sci, Shanghai Inst Infect Dis & Biosecur, State Key Lab Genet Engn, Fudan University, Shanghai, China
Interests: coronavirus; HIV-1; antibody; vaccine

Special Issue Information

Dear Colleagues,

All coronaviruses have the potential to undergo “recombination”, when two different viruses or lineages simultaneously infect the same cell, especially in immunocompromised people. Recombination events among SARS-CoV and MERSCoV are well-documented; however, it is difficult to detect the recombination of SARS-CoV-2 variants due to their high sequence similarity. The Delta and Omicron recombinations have been reported and referred to as Deltacron, and recombinant variants of Omicron sublineages such as XE (BA.1-BA.2) and XBB.1.5 (BA.2.10.1-BA.2.75) have also attracted widespread attention. This rare phenomenon may affect the characteristics of the virus, including its transimission rate, disease severity, or immune evasion ability. As such, it is imperative to monitor and evaluate the genome recombination of SARS-CoV-2 to provide valuable insights regarding epidemic and transmission trends.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. Evolution and epidemics of SARS-CoV-2 recombinant variants;
  2. Real-time evaluation of the risk of recombinant variants;
  3. The virological characteristics of recombinant variants, such as their transmissibility, immune evasion, ACE2 binding affinity, infectivity, fusogenicity, structural information, and pathogenicity in an animal model;
  4. Effective vaccines/antibodies/drugs against recombinant variant.

I look forward to receiving your contributions.

Dr. Pengfei Wang
Guest Editor

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Keywords

  • SARS-CoV-2
  • recombinant variant
  • genomic surveillance
  • vaccine
  • neutralizing antibody
  • antiviral drug
  • virological characteristic
  • immune evasion
  • evolution

Published Papers (6 papers)

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Research

11 pages, 847 KiB  
Article
Development and Clinical Performance of InteliSwab® COVID-19 Rapid Test: Evaluation of Antigen Test for the Diagnosis of SARS-CoV-2 and Analytical Sensitivity to Detect Variants of Concern Including Omicron and Subvariants
by Mark J. Fischl, Janean Young, Keith Kardos, Michele Roehler, Tiffany Miller, Melinda Wooten, Natalie Holmes, Nicole Gula, Mia Baglivo, Justin Steen, Nori Zelenz, Antony George Joyee, Vincent Munster, Zack Weishampel, Claude Kwe Yinda, Kevin G. Rouse, Cathy Gvozden, David Wever, Giralt Yanez, Marc Anderson, Song Yu, Brian Bearie, Stephen Young and Jody D. Berryadd Show full author list remove Hide full author list
Viruses 2024, 16(1), 61; https://doi.org/10.3390/v16010061 - 29 Dec 2023
Viewed by 1049
Abstract
Background and objectives: Timely detection of SARS-CoV-2 infection with subsequent contact tracing and rapid isolation are considered critical to containing the pandemic, which continues with the emergence of new variants. Hence, there is an ongoing need for reliable point-of-care antigen rapid diagnostic tests [...] Read more.
Background and objectives: Timely detection of SARS-CoV-2 infection with subsequent contact tracing and rapid isolation are considered critical to containing the pandemic, which continues with the emergence of new variants. Hence, there is an ongoing need for reliable point-of-care antigen rapid diagnostic tests (Ag-RDT). This report describes the development, evaluation, and analytical sensitivity of the diagnostic performance of the InteliSwab® COVID-19 Rapid Test. Methods: Samples from 165 symptomatic subjects were tested with InteliSwab® and the results were compared to RT-PCR to determine the antigen test performance. The analytical sensitivity of InteliSwab® for the detection of different variants was assessed by limit of detection (LOD) determination using recombinant nucleocapsid proteins (NPs) and testing with virus isolates. Western immunoblot independently confirmed that each monoclonal Ab is capable of binding to all variants tested thus far. Results: The overall positivity rate by RT-PCR was 37% for the 165 symptomatic subjects. Based on RT-PCR results as the reference standard, InteliSwab® showed clinical sensitivity and specificity of 85.2% (95% CI, 74.3–92.0%) and 98.1% (95% CI, 93.3–99.7%), respectively. The overall agreement was 93.3% (Kappa index value 0.85; 95% CI, 0.77–0.74) between RT-PCR and InteliSwab® test results. Furthermore, the evaluation of analytical sensitivity for different SARS-CoV-2 variants by InteliSwab® was comparable in the detection of all the variants tested, including Omicron subvariants, BA.4, BA.5, and BQ.1. Conclusions: Due to the surge of infections caused by different variants from time to time, there is a critical need to evaluate the sensitivity of rapid antigen-detecting tests for new variants. The study findings showed the robust diagnostic performance of InteliSwab® and analytical sensitivity in detecting different SARS-CoV-2 variants, including the Omicron subvariants. With the integrated swab and excellent sensitivity and variant detection, this test has high potential as a point-of-care Ag-RDT in various settings when molecular assays are in limited supply and rapid diagnosis of SARS-CoV-2 is necessary. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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14 pages, 2876 KiB  
Article
Effect of SARS-CoV-2 Breakthrough Infection on HIV Reservoirs and T-Cell Immune Recovery in 3-Dose Vaccinated People Living with HIV
by Meng-Meng Qu, Bing Song, Bao-Peng Yang, Zerui Wang, Minrui Yu, Yi Zhang, Chao Zhang, Jin-Wen Song, Xing Fan, Ruonan Xu, Ji-Yuan Zhang, Chun-Bao Zhou, Fengxia Du, Fu-Sheng Wang, Hui-Huang Huang and Yan-Mei Jiao
Viruses 2023, 15(12), 2427; https://doi.org/10.3390/v15122427 - 14 Dec 2023
Viewed by 984
Abstract
People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory [...] Read more.
People living with human immunodeficiency virus (PLWH) are a vulnerable population with a higher risk of severe coronavirus disease 2019 (COVID-19); therefore, vaccination is recommended as a priority. Data on viral reservoirs and immunologic outcomes for PLWH breakthrough infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are currently limited. In this study, we investigated the effects of SARS-CoV-2 breakthrough infection on hematological parameters, human immunodeficiency virus (HIV) reservoir size, and T-cell recovery in PLWH receiving antiretroviral therapy (ART) after SARS-CoV-2 booster vaccination. The results indicated that during breakthrough infection, booster vaccination with homologous and heterologous vaccines was safe in PLWH after receiving two doses of inactivated vaccination. The absolute CD4 counts decreased in the heterologous group, whereas the CD8 counts decreased in the homologous booster group after breakthrough infection in PLWH. Breakthrough infection increased HIV reservoirs and was associated with increased T-cell activation in PLWH who received virally suppressed ART and a 3-dose vaccination. According to our data, the breakthrough infection of SARS-CoV-2 may put PLWH at a greater risk for increased HIV reservoirs, even if these individuals were virally suppressed with ART after 3-dose SARS-CoV-2 vaccination. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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16 pages, 3334 KiB  
Article
Analyses of S Protein Homology Using the Genomes of SARS-CoV-2 Specimens Unveil Missing Links in the Temporal Order of Mutations in Its Variants
by Ruri Kitayama and Yoshiyuki Ogata
Viruses 2023, 15(11), 2182; https://doi.org/10.3390/v15112182 - 30 Oct 2023
Viewed by 770
Abstract
(1) Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the evolutionary traits of its variants have been revealed. However, the temporal order of the majority of mutations harbored by variants after the closest ancestors (or precursors), as “missing links”, [...] Read more.
(1) Background: Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the evolutionary traits of its variants have been revealed. However, the temporal order of the majority of mutations harbored by variants after the closest ancestors (or precursors), as “missing links”, remains unclear. In this study, we aimed to unveil such missing links based on analyses of S protein homology by focusing on specimens with incomplete sets of S protein mutations in a variant. (2) Methods: Prevariant and postvariant mutations were defined as those before and after the variant’s development, respectively. A total of 6,758,926 and 14,519,521 genomes were obtained from the National Center for Biotechnology Information and the GISAID initiative, respectively, and S protein mutations were detected based on BLASTN analyses. (3) Results: The temporal order of prevariant mutations harbored by 12 variants was deduced. In particular, the D950N mutation in the Mu variant shows V-shaped mutation transitions, in which multiple routes of evolution were combined and resulted in the formation of a V-shaped transition, indicating recombination. (4) Conclusions: Many genome data for SARS-CoV-2 unveiled the candidate precursors of Mu variant based on a data-driven approach to its prevariant mutations in each nation. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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38 pages, 8890 KiB  
Article
Comparative Analysis of Conformational Dynamics and Systematic Characterization of Cryptic Pockets in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 Spike Complexes with the ACE2 Host Receptor: Confluence of Binding and Structural Plasticity in Mediating Networks of Conserved Allosteric Sites
by Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao and Gennady Verkhivker
Viruses 2023, 15(10), 2073; https://doi.org/10.3390/v15102073 - 10 Oct 2023
Cited by 2 | Viewed by 1383
Abstract
In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 [...] Read more.
In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results are significant for understanding the functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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16 pages, 9029 KiB  
Article
CovidShiny: An Integrated Web Tool for SARS-CoV-2 Mutation Profiling and Molecular Diagnosis Assay Evaluation In Silico
by Shaoqian Ma, Gezhi Xiao, Xusheng Deng, Mengsha Tong, Jialiang Huang, Qingge Li and Yongyou Zhang
Viruses 2023, 15(10), 2017; https://doi.org/10.3390/v15102017 - 28 Sep 2023
Viewed by 1163
Abstract
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuing to evolve and accumulate mutations. While various bioinformatics tools have been developed for SARS-CoV-2, a well-curated mutation-tracking database integrated with in silico evaluation for molecular [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuing to evolve and accumulate mutations. While various bioinformatics tools have been developed for SARS-CoV-2, a well-curated mutation-tracking database integrated with in silico evaluation for molecular diagnostic assays is currently unavailable. To address this, we introduce CovidShiny, a web tool that integrates mutation profiling, in silico evaluation, and data download capabilities for genomic sequence-based SARS-CoV-2 assays and data download. It offers a feasible framework for surveilling the mutation of SARS-CoV-2 and evaluating the coverage of the molecular diagnostic assay for SARS-CoV-2. With CovidShiny, we examined the dynamic mutation pattern of SARS-CoV-2 and evaluated the coverage of commonly used assays on a large scale. Based on our in silico analysis, we stress the importance of using multiple target molecular diagnostic assays for SARS-CoV-2 to avoid potential false-negative results caused by viral mutations. Overall, CovidShiny is a valuable tool for SARS-CoV-2 mutation surveillance and in silico assay design and evaluation. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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21 pages, 3972 KiB  
Article
Omicron Coronavirus: pH-Dependent Electrostatic Potential and Energy of Association of Spike Protein to ACE2 Receptor
by Svetlana H. Hristova and Alexandar M. Zhivkov
Viruses 2023, 15(8), 1752; https://doi.org/10.3390/v15081752 - 17 Aug 2023
Cited by 3 | Viewed by 1226
Abstract
The association of the S-protein of the SARS-CoV-2 beta coronavirus to ACE2 receptors of the human epithelial cells determines its contagiousness and pathogenicity. We computed the pH-dependent electric potential on the surface of the interacting globular proteins and pH-dependent Gibbs free energy at [...] Read more.
The association of the S-protein of the SARS-CoV-2 beta coronavirus to ACE2 receptors of the human epithelial cells determines its contagiousness and pathogenicity. We computed the pH-dependent electric potential on the surface of the interacting globular proteins and pH-dependent Gibbs free energy at the association of the wild-type strain and the omicron variant. The calculated isoelectric points of the ACE2 receptor (pI 5.4) and the S-protein in trimeric form (pI 7.3, wild type), (pI 7.8, omicron variant), experimentally verified by isoelectric focusing, show that at pH 6–7, the S1–ACE2 association is conditioned by electrostatic attraction of the oppositely charged receptor and viral protein. The comparison of the local electrostatic potentials of the omicron variant and the wild-type strain shows that the point mutations alter the electrostatic potential in a relatively small area on the surface of the receptor-binding domain (RBD) of the S1 subunit. The appearance of seven charge-changing point mutations in RBD (equivalent to three additional positive charges) leads to a stronger S1–ACE2 association at pH 5.5 (typical for the respiratory tract) and a weaker one at pH 7.4 (characteristic of the blood plasma); this reveals the reason for the higher contagiousness but lower pathogenicity of the omicron variant in comparison to the wild-type strain. Full article
(This article belongs to the Special Issue Recombinant Variants of SARS-CoV-2)
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