Evolutionary deletions within the SARS-CoV-2 genome as signature trends for virus fitness and adaptation

Jeronimo, Pedro Miguel Carneiro; Aksenen, Cleber Furtado; Duarte, Igor Oliveira; Lins, Roberto D.; Miyajima, Fabio

doi:10.1128/jvi.01404-23

Cited by 3 publications

(2 citation statements)

References 62 publications

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“…These advantages may include but are not limited to better evasion in the host immune response or enhanced transmission under specific environmental conditions, which may be favored by natural selection and retained in the evolutionary process. As ongoing research continues to isolate and identify more ASFV strains, an increasing number of attenuated strains with potential vaccine value are emerging worldwide [ 57 ]. However, mutations may also lead to the development of strains that possess enhanced immune evasion and more covert transmission advantages.…”

Section: Main Trends In the Genetic Evolution Of Asfvmentioning

confidence: 99%

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects

Chen,

Wang,

Luo

et al. 2024

Viruses

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African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.

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Section: Main Trends In the Genetic Evolution Of Asfvmentioning

confidence: 99%

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects

Chen,

Wang,

Luo

et al. 2024

Viruses

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“…NAbs induced by NTD also have been shown responsible for the cross-neutralization against BA.5 in BA.2 BTI convalescents [11]. Concurrently, NTD continues to evolve, notably through insertions and deletions of multiple amino acids, diverging from RBD mutations [12][13][14][15]. Within Omicron subvariants, BA.2 exhibited distinct NTD mutations compared to BA.1, which has the notable HV69-70del and 143-145del.…”

Section: Introductionmentioning

confidence: 99%

Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain

Niu,

Li,

Wang

et al. 2024

Preprint

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A multitude of functional mutations continue to emerge on the N-terminal domain (NTD) of the spike protein in SARS-CoV-2 Omicron subvariants. Understanding the immunogenicity of Omicron NTD and the properties of antibodies elicited by it is crucial for comprehending the impact of NTD mutations on viral fitness and guiding vaccine design. In this study, we find that most of NTD-targeting antibodies isolated from individuals with BA.5/BF.7 breakthrough infection (BTI) are ancestral (wildtype or WT)-reactive and non-neutralizing. Surprisingly, we identified five ultra-potent neutralizing antibodies (NAbs) that can only bind to Omicron but not WT NTD. Structural analysis revealed that they bind to a unique epitope on the N1/N2 loop of NTD and interact with the receptor-binding domain (RBD) via the light chain. These Omicron-specific NAbs achieve neutralization through ACE2 competition and blockage of ACE2-mediated S1 shedding. However, BA.2.86 and BA.2.87.1, which carry insertions or deletions on the N1/N2 loop, can evade these antibodies. Together, we provided a detailed map of the NTD-targeting antibody repertoire in the post-Omicron era, demonstrating their vulnerability to NTD mutations enabled by its evolutionary flexibility, despite their potent neutralization. These results highlighted the importance of considering the immunogenicity of NTD in vaccine design.Author SummaryCOVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major global public health concern four years after its emergence. The N-terminal domain (NTD) is a critical component of the spike glycoprotein, which is pivotal for SARS-CoV-2 cellular entry and serves as a primary target for antibody therapeutics and vaccine development. Characterizing the properties of antibodies elicited by NTD of Omicron sublineages is crucial for understanding viral evolution and guiding vaccine design. Here, we show that Omicron infection after vaccination induces majorly non-neutralizing NTD antibodies. Still, we identified a class of ultra-potent neutralizing antibodies (NAbs) which specifically bind to the NTD of Omicron sublineages. These NAbs neutralize the virus by competing with ACE2 and blocking ACE2-mediated S1 shedding. Structural analyses reveal that these antibodies target a unique epitope on the N1/N2 loop of NTD, and intriguingly interact with the receptor-binding domain (RBD) of spike glycoprotein. This class of NAbs with the special binding pattern, are escaped by BA.2.86 and BA.2.87.1 sublineages, shedding light on the role of recently emerged mutations in the N1/N2 loop of NTD. Our findings provide fresh insights into the immunogenicity of Omicron NTD, highlighting its capacity for antibody evasion due to its evolutionary flexibility. This underscores the importance of carefully considering the NTD component in vaccine design.

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Enhancing SARS-CoV-2 Lineage surveillance through the integration of a simple and direct qPCR-based protocol adaptation with established machine learning algorithms

Aksenen,

Ferreira,

Jeronimo

et al. 2024

Preprint

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The emergence of the SARS-CoV-2 and continuous spread of its descendent lineages have posed unprecedented challenges to the global public healthcare system. Here we present an inclusive approach integrating genomic sequencing and qPCR-based protocols to increment monitoring of variant Omicron sublineages. Viral RNA samples were fast tracked for genomic surveillance following the detection of SARS-CoV-2 by diagnostic laboratories or public health network units in Ceara (Brazil) and analyzed using paired-end sequencing and integrative genomic analysis. Validation of a key structural variation was conducted with gel electrophoresis for the presence of a specific ORF7a deletion within the “BE.9” lineages. A simple intercalating dye-based qPCR assay protocol was tested and optimized through the repositioning primers from the ARTIC v.4.1 amplicon panel, which was able to distinguish between “BE.9” and “non-BE.9” lineages, particularly BQ.1. Three ML models were trained with the melting curve of the intercalating dye-based qPCR that enabled lineage assignment with elevated accuracy. Amongst them, the Support Vector Machine (SVM) model had the best performance and after fine-tuning showed ∼96.52% (333/345) accuracy in comparison to the test dataset. The integration of these methods may allow rapid assessment of emerging variants and increment molecular surveillance strategies, especially in resource-limited settings. Our approach not only provides a cost-effective alternative to complement traditional sequencing methods but also offers a scalable analytical solution for enhanced monitoring of SARS-CoV-2 variants for other laboratories through easy-to-train ML algorithms, thus contributing to global efforts in pandemic control.

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Evolutionary deletions within the SARS-CoV-2 genome as signature trends for virus fitness and adaptation

Cited by 3 publications

References 62 publications

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects

Genetic Variations of African Swine Fever Virus: Major Challenges and Prospects

Omicron-specific ultra-potent SARS-CoV-2 neutralizing antibodies targeting the N1/N2 loop of Spike N-terminal domain

Enhancing SARS-CoV-2 Lineage surveillance through the integration of a simple and direct qPCR-based protocol adaptation with established machine learning algorithms

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