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Genetic Variability and Molecular Evolution of SARS-CoV-2

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 20 February 2025 | Viewed by 11388

Special Issue Editors

Special Issue Information

Dear Colleagues,

The proposed Special Issue, titled "Genetic Variability and Molecular Evolution of SARS-CoV-2," aims to collate significant scientific contributions made by leading international experts in the molecular evolution of SARS-CoV-2. Due to its unique biological characteristics, SARS-CoV-2 has exhibited a high propensity for molecular changes and adaptation. Consequently, numerous variants, subvariants, and recombinants of SARS-CoV-2 have emerged since the beginning of the pandemic. Several molecular surveys have been conducted and published over the years, revealing varying expansion capabilities and molecular characteristics among lineages. However, all studies emphasize the necessity for continuous and uninterrupted genome-based surveillance. This approach would provide the most comprehensive understanding of the current predominant lineage’s genomic composition. Indeed, constant monitoring is crucial for identifying and predicting significant changes in genomic composition, enabling the development of appropriate action plans.

Dr. Fabio Scarpa
Prof. Dr. Massimo Ciccozzi
Guest Editors

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Keywords

  • SARS-CoV-2 phylogenomics
  • genetics
  • molecular epidemiology

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Published Papers (6 papers)

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Research

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21 pages, 3434 KiB  
Article
Progressive Evolutionary Dynamics of Gene-Specific ω Led to the Emergence of Novel SARS-CoV-2 Strains Having Super-Infectivity and Virulence with Vaccine Neutralization
by Amit K. Maiti
Int. J. Mol. Sci. 2024, 25(12), 6306; https://doi.org/10.3390/ijms25126306 - 7 Jun 2024
Viewed by 912
Abstract
An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, [...] Read more.
An estimation of the proportion of nonsynonymous to synonymous mutation (dn/ds, ω) of the SARS-CoV-2 genome would indicate the evolutionary dynamics necessary to evolve into novel strains with increased infection, virulence, and vaccine neutralization. A temporal estimation of ω of the whole genome, and all twenty-nine SARS-CoV-2 genes of major virulent strains of alpha, delta and omicron demonstrates that the SARS-CoV-2 genome originally emerged (ω ~ 0.04) with a strong purifying selection (ω < 1) and reached (ω ~ 0.85) in omicron towards diversifying selection (ω > 1). A marked increase in the ω occurred in the spike gene from alpha (ω = 0.2) to omicron (ω = 1.97). The ω of the replication machinery genes including RDRP, NSP3, NSP4, NSP7, NSP8, NSP10, NSP13, NSP14, and ORF9 are markedly increased, indicating that these genes/proteins are yet to be evolutionary stabilized and are contributing to the evolution of novel virulent strains. The delta-specific maximum increase in ω in the immunomodulatory genes of NSP8, NSP10, NSP16, ORF4, ORF5, ORF6, ORF7A, and ORF8 compared to alpha or omicron indicates delta-specific vulnerabilities for severe COVID-19 related hospitalization and death. The maximum values of ω are observed for spike (S), NSP4, ORF8 and NSP15, which indicates that the gene-specific temporal estimation of ω identifies specific genes for its super-infectivity and virulency that could be targeted for drug development. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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14 pages, 4459 KiB  
Article
Comparative Bioinformatic Analysis Reveals Conserved Regions in SARS-CoV-2 Genome for RAPID Pandemic Response
by Marcela Viviana Karpuj, D. R. Shaytov, Yonat Shemer-Avni, Michael Gideon, Zakharia M. Frenkel and Sarit Sivan
Int. J. Mol. Sci. 2024, 25(11), 5764; https://doi.org/10.3390/ijms25115764 - 25 May 2024
Viewed by 1276
Abstract
In the face of the SARS-CoV-2 pandemic, characterized by the virus’s rapid mutation rates, developing timely and targeted therapeutic and diagnostic interventions presents a significant challenge. This study utilizes bioinformatic analyses to pinpoint conserved genomic regions within SARS-CoV-2, offering a strategic advantage in [...] Read more.
In the face of the SARS-CoV-2 pandemic, characterized by the virus’s rapid mutation rates, developing timely and targeted therapeutic and diagnostic interventions presents a significant challenge. This study utilizes bioinformatic analyses to pinpoint conserved genomic regions within SARS-CoV-2, offering a strategic advantage in the fight against this and future pathogens. Our approach has enabled the creation of a diagnostic assay that is not only rapid, reliable, and cost-effective but also possesses a remarkable capacity to detect a wide array of current and prospective variants with unmatched precision. The significance of our findings lies in the demonstration that focusing on these conserved genomic sequences can significantly enhance our preparedness for and response to emerging infectious diseases. By providing a blueprint for the development of versatile diagnostic tools and therapeutics, this research paves the way for a more effective global pandemic response strategy. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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21 pages, 2536 KiB  
Article
Multiple Lines of Evidence Support 199 SARS-CoV-2 Positively Selected Amino Acid Sites
by Pedro Ferreira, Ricardo Soares, Hugo López-Fernández, Noé Vazquez, Miguel Reboiro-Jato, Cristina P. Vieira and Jorge Vieira
Int. J. Mol. Sci. 2024, 25(4), 2428; https://doi.org/10.3390/ijms25042428 - 19 Feb 2024
Viewed by 1604
Abstract
SARS-CoV-2 amino acid variants that contribute to an increased transmissibility or to host immune system escape are likely to increase in frequency due to positive selection and may be identified using different methods, such as codeML, FEL, FUBAR, and MEME. Nevertheless, when using [...] Read more.
SARS-CoV-2 amino acid variants that contribute to an increased transmissibility or to host immune system escape are likely to increase in frequency due to positive selection and may be identified using different methods, such as codeML, FEL, FUBAR, and MEME. Nevertheless, when using different methods, the results do not always agree. The sampling scheme used in different studies may partially explain the differences that are found, but there is also the possibility that some of the identified positively selected amino acid sites are false positives. This is especially important in the context of very large-scale projects where hundreds of analyses have been performed for the same protein-coding gene. To account for these issues, in this work, we have identified positively selected amino acid sites in SARS-CoV-2 and 15 other coronavirus species, using both codeML and FUBAR, and compared the location of such sites in the different species. Moreover, we also compared our results to those that are available in the COV2Var database and the frequency of the 10 most frequent variants and predicted protein location to identify those sites that are supported by multiple lines of evidence. Amino acid changes observed at these sites should always be of concern. The information reported for SARS-CoV-2 can also be used to identify variants of concern in other coronaviruses. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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22 pages, 4023 KiB  
Article
Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study
by Angela Lu, Brandon Ebright, Aditya Naik, Hui L. Tan, Noam A. Cohen, Jean-Marie C. Bouteiller, Gianluca Lazzi, Stan G. Louie, Mark S. Humayun and Isaac Asante
Int. J. Mol. Sci. 2024, 25(4), 2061; https://doi.org/10.3390/ijms25042061 - 8 Feb 2024
Cited by 1 | Viewed by 3019
Abstract
The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive [...] Read more.
The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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13 pages, 2186 KiB  
Article
Integrative Genome-Based Survey of the SARS-CoV-2 Omicron XBB.1.16 Variant
by Fabio Scarpa, Ilenia Azzena, Alessandra Ciccozzi, Marta Giovanetti, Chiara Locci, Marco Casu, Pier Luigi Fiori, Alessandra Borsetti, Eleonora Cella, Miriana Quaranta, Stefano Pascarella, Daria Sanna and Massimo Ciccozzi
Int. J. Mol. Sci. 2023, 24(17), 13573; https://doi.org/10.3390/ijms241713573 - 1 Sep 2023
Cited by 5 | Viewed by 1552
Abstract
The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the [...] Read more.
The XBB.1.16 SARS-CoV-2 variant, also known as Arcturus, is a recent descendant lineage of the recombinant XBB (nicknamed Gryphon). Compared to its direct progenitor, XBB.1, XBB.1.16 carries additional spike mutations in key antigenic sites, potentially conferring an ability to evade the immune response compared to other circulating lineages. In this context, we conducted a comprehensive genome-based survey to gain a detailed understanding of the evolution and potential dangers of the XBB.1.16 variant, which became dominant in late June. Genetic data indicates that the XBB.1.16 variant exhibits an evolutionary background with limited diversification, unlike dangerous lineages known for rapid changes. The evolutionary rate of XBB.1.16, which amounts to 3.95 × 10−4 subs/site/year, is slightly slower than that of its direct progenitors, XBB and XBB.1.5, which have been circulating for several months. A Bayesian Skyline Plot reconstruction suggests that the peak of genetic variability was reached in early May 2023, and currently, it is in a plateau phase with a viral population size similar to the levels observed in early March. Structural analyses indicate that, overall, the XBB.1.16 variant does not possess structural characteristics markedly different from those of the parent lineages, and the theoretical affinity for ACE2 does not seem to change among the compared variants. In conclusion, the genetic and structural analyses of SARS-CoV-2 XBB.1.16 do not provide evidence of its exceptional danger or high expansion capability. Detected differences with previous lineages are probably due to genetic drift, which allows the virus constant adaptability to the host, but they are not necessarily connected to a greater danger. Nevertheless, continuous genome-based monitoring is essential for a better understanding of its descendants and other lineages. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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Review

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18 pages, 2498 KiB  
Review
Properties and Mechanisms of Deletions, Insertions, and Substitutions in the Evolutionary History of SARS-CoV-2
by Igor B. Rogozin, Andreu Saura, Eugenia Poliakov, Anastassia Bykova, Abiel Roche-Lima, Youri I. Pavlov and Vyacheslav Yurchenko
Int. J. Mol. Sci. 2024, 25(7), 3696; https://doi.org/10.3390/ijms25073696 - 26 Mar 2024
Cited by 2 | Viewed by 2144
Abstract
SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of [...] Read more.
SARS-CoV-2 has accumulated many mutations since its emergence in late 2019. Nucleotide substitutions leading to amino acid replacements constitute the primary material for natural selection. Insertions, deletions, and substitutions appear to be critical for coronavirus’s macro- and microevolution. Understanding the molecular mechanisms of mutations in the mutational hotspots (positions, loci with recurrent mutations, and nucleotide context) is important for disentangling roles of mutagenesis and selection. In the SARS-CoV-2 genome, deletions and insertions are frequently associated with repetitive sequences, whereas C>U substitutions are often surrounded by nucleotides resembling the APOBEC mutable motifs. We describe various approaches to mutation spectra analyses, including the context features of RNAs that are likely to be involved in the generation of recurrent mutations. We also discuss the interplay between mutations and natural selection as a complex evolutionary trend. The substantial variability and complexity of pipelines for the reconstruction of mutations and the huge number of genomic sequences are major problems for the analyses of mutations in the SARS-CoV-2 genome. As a solution, we advocate for the development of a centralized database of predicted mutations, which needs to be updated on a regular basis. Full article
(This article belongs to the Special Issue Genetic Variability and Molecular Evolution of SARS-CoV-2)
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