Enhanced Detection and Molecular Modeling of Adaptive Mutations in SARS-CoV-2 Coding and Non-Coding Regions Using the c/µ Test DOI Creative Commons
Nicholas J. Paradis, Chun Wu

Virus Evolution, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 1, 2024

Accurately identifying mutations under beneficial selection in viral genomes is crucial for understanding their molecular evolution and pathogenicity. Traditional methods like the Ka/Ks test, which assesses non-synonymous (Ka) versus synonymous (Ks) substitution rates, assume that substitutions at sites are neutral thus equal to mutation rate (µ). Yet, evidence suggests translated regions (TRs) untranslated (UTRs) can be strong (Ks > µ) strongly conserved ≈ 0), leading false predictions of adaptive from codon-by-codon analysis. Our previous work used a relative test (c/µ, c: UTR/TR, µ: rate) identify SARS-CoV-2 genome without neutrality assumption sites. This study refines c/µ by optimizing µ value, smaller set nucleotide amino acid both UTR (11 with 3) TR (69 nonsynonymous sites: 3 2.5; 107 Ks/µ 3). Encouragingly, top two 70% had reported or predicted effects literature. Molecular modeling some critical proteins (S, NSP11, NSP5) was carried out elucidate possible mechanism adaptivity.

Language: Английский

Whole-Genome Sequencing and Mutation Analyses of SARS-CoV-2 Isolates from Indonesia DOI Creative Commons
Sukma Oktavianthi, Aksar Chair Lages,

Rinaldy Kusuma

et al.

Pathogens, Journal Year: 2024, Volume and Issue: 13(4), P. 279 - 279

Published: March 25, 2024

The SARS-CoV-2 infection that caused the COVID-19 pandemic has become a significant public health concern. New variants with distinct mutations have emerged, potentially impacting its infectivity, immune evasion capacity, and vaccine response. A whole-genome sequencing study of 292 isolates collected from selected regions Indonesia between January October 2021 was performed to identify distribution common in Indonesia. During January–April 2021, Indonesian lineages B.1.466.2 B.1.470 dominated, but May Delta’s AY.23 lineage outcompeted them. An analysis 7515 published sequences June 2022 revealed decline Delta November followed by emergence Omicron December 2021. We identified C241T (5′UTR), P314L (NSP12b), F106F (NSP3), D614G (Spike) all sequences. other substitutions included P681R (76.4%) T478K (60%) Spike, D377Y Nucleocapsid (61%), I82T Membrane proteins. Breakthrough prolonged viral shedding cases were associated carrying Spike T19R, G142D, L452R, T478K, D614G, P681R, D950N, V1264L mutations. dynamic highlights importance continuous genomic surveillance monitoring identifying potential strains leading disease outbreaks.

Language: Английский

Citations

7
Molecular Epidemiology of SARS-CoV-2 during Five COVID-19 Waves and the Significance of Low-Frequency Lineages DOI Creative Commons
Kathleen Subramoney,

Nkhensani Mtileni,

Jennifer Giandhari

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(5), P. 1194 - 1194

Published: May 18, 2023

SARS-CoV-2 lineages and variants of concern (VOC) have gained more efficient transmission immune evasion properties with time. We describe the circulation VOCs in South Africa potential role low-frequency on emergence future lineages. Whole genome sequencing was performed samples from Africa. Sequences were analysed Nextstrain pangolin tools Stanford University Coronavirus Antiviral & Resistance Database. In 2020, 24 detected, B.1 (3%; 8/278), B.1.1 (16%; 45/278), B.1.1.348 B.1.1.52 (5%; 13/278), C.1 (13%; 37/278) C.2 (2%; 6/278) circulating during first wave. Beta emerged late dominating second wave infection. continued to circulate at low frequencies 2021 re-emerged 2022. outcompeted by Delta 2021, which thereafter Omicron sub-lineages 4th 5th waves Several significant mutations identified also detected lineages, including S68F (E protein); I82T (M P13L, R203K G204R/K (N R126S (ORF3a); P323L (RdRp); N501Y, E484K, D614G, H655Y N679K (S protein). Low-frequency variants, together circulating, may lead convergence that increase transmissibility, infectivity escape vaccine-induced or natural host immunity.

Language: Английский

Citations

11
Unraveling the genetic evolution of SARS-CoV-2 Recombinants using mutational dynamics across the different lineages DOI Creative Commons

Varsha Ravi,

Uzma Shamim,

Md Abuzar Khan

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 10

Published: Jan. 15, 2024

Introduction Recombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events viral This study introspects phenomenon of genome tracing footprint prominent lineages at different time points in context on-going evolution and emergence Recombinants. Method Whole sequencing was carried out 2,516 (discovery cohort) 1,126 (validation using nasopharyngeal samples collected between period March 2020 to August 2022, part program. The sequences were classified according prevailing India respective points. Results Mutational diversity abundance evaluation across 12 identified 58 harboring least number mutations ( n = 111), with 14 low-frequency unique major chunk coming from BA.2. spontaneously/dynamically increasing decreasing trends highlight loss Recombinants that associated replication efficiency, infectivity, disease severity, rendering them functionally low infectivity pathogenicity. Linkage disequilibrium (LD) analysis revealed comprising LD blocks BA.1, BA.2, found minor alleles or previous variant samples, especially Pre-VOC. Moreover, dissipation size well decay along high negative regression coefficient (R squared) value demonstrated Omicron BA.1 BA.2 lineages, which corroborated breakpoint analysis. Conclusion Together, findings help understand after sustenance adaptability, maintain epidemic spread host population already immunity levels.

Language: Английский

Citations

4
Development of Monoclonal Antibodies Against SARS-CoV-2 Nucleocapsid Protein for COVID-19 Antigen Detection DOI

Maurine Mumo Mutua,

Bernard N. Kanoi, Steven Ger Nyanjom

et al.

Published: April 14, 2025

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic underscored the global need for reliable diagnostic tools with quick turnaround time effective patient management and mitigation of virus spread. This study aimed to express severe acute respiratory syndrome 2 (SARS-CoV-2) nucleocapsid protein produce monoclonal antibodies (mAbs) against expressed protein. Methods Following successful expression purification His-tagged SARS-CoV-2 N using a wheat germ cell-free system (WGCFS), BALB/c mice were immunized, generated hybridomas screened mAb production. Indirect sandwich ELISA used screen reactivity antibody both our recombinant antigen commercial antigen. mAbs also assessed their performance RT-PCR confirmed positive samples varying cycle threshold (CT) values specificity intracellular fluid (ICF) other viruses. Results Our demonstrated high antigen, Beta Omicron variants. There was no significant difference in binding affinity (p = 0.12) 0.072) antigens. detected from clinical CT exhibited cross-reactivity Conclusion We successfully leveraging WGCFS resource-limited setting. had making it suitable candidate detection kit development. Beyond diagnostics, holds potential therapeutic applications as well use environmental surveillance platforms.

Language: Английский

Citations

0
Genomic Surveillance and Mutation Analysis of SARS-CoV-2 Variants among Patients in Saudi Arabia DOI Creative Commons
Feda A. Alsuwairi, Asma N. Alsaleh, Dalia Obeid

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(3), P. 467 - 467

Published: Feb. 26, 2024

The genome of severe acute respiratory coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has undergone a rapid evolution, resulting in emergence multiple SARS-CoV-2 variants with amino acid changes. This study aimed to sequence whole and detect present specimens from Saudi Arabia. Furthermore, we sought analyze characterize changes various proteins identified variants. A total 1161 samples patients diagnosed COVID-19 Arabia, between 1 April 2021 31 July 2023, were analyzed. Whole sequencing was employed variant identification mutation analysis. statistical analysis performed using Statistical Analytical Software SAS, version 9.4, GraphPad, 9.0. twenty-three subvariants within population, Omicron BA.1 (21K) (37.0%) Delta (21J) (12%) being most frequently detected. Notably, exhibited higher mean rate. Amino mutations observed twelve proteins. Among these, spike (S), ORF1a, nucleocapsid (N), ORF1b showed frequency compared other viral S protein highest incidence (47.6%). Conversely, ORF3a, ORF8, ORF7a, ORF6, ORF7b appeared more conserved, demonstrating lowest percentage mutations. investigation structural regions revealed N-terminal S1 subunit harbor mutations, while domain envelope (E) displayed frequency. provides insights into genetic diversity SARS-CoV-2, underscoring need further research comprehend its evolution occurrence These findings are pertinent development testing approaches, therapeutics, vaccine strategies.

Language: Английский

Citations

3
Strategies Used by SARS-CoV-2 To Evade the Innate Immune System in an Evolutionary Perspective DOI Creative Commons
Hong Fan, Mingfu Tian, Siyu Liu

et al.

Pathogens, Journal Year: 2024, Volume and Issue: 13(12), P. 1117 - 1117

Published: Dec. 17, 2024

By the end of 2019, COVID-19 pandemic, resulting from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), had diffused widely across globe, with 770 million infected individuals and over 7 deaths reported. In addition to its high infectivity pathogenicity rapid mutation rate, unique capacity SARS-CoV-2 circumvent immune system has also contributed widespread nature this pandemic. elicits onset innate activation initiates antiviral responses once it host. While battling host’s responses, established many countermeasures evade attack clearance. As exploration continues, substantial evidence revealed that 29 proteins synthesized by genome are integral viral infection process. They not only facilitate replication transmission, but assist in escaping defenses, positioning them as promising therapeutic targets have attracted considerable attention recent studies. This review summarizes manner which interfaces system, a particular focus on continuous evolution implications mutations.

Language: Английский

Citations

1
Characteristics and clinical manifestations of patients, including organ transplant patients, during the surge of JN.1: Insights from Saudi Arabia DOI Creative Commons
Dalia Obeid, Ahmed A. Al‐Qahtani, Reem S. Almaghrabi

et al.

Journal of Infection and Public Health, Journal Year: 2024, Volume and Issue: 17(7), P. 102452 - 102452

Published: May 16, 2024

Amidst the persistent global health threat posed by evolving SARS-CoV-2 virus throughout four-year-long COVID-19 pandemic, focus has now turned to Omicron variant and its subvariant, JN.1, which rapidly disseminated worldwide. This study reports on characteristics clinical manifestations of patients during surge JN.1 in Saudi Arabia; it also investigates evolution variants organ transplant identifies patient risk factors.

Language: Английский

Citations

0
Characterization of the viral genome of Omicron variants of SARS-CoV-2 circulating in Tripura, a remote frontier state in Northeastern India DOI
Ankan Chakrabarti, Saikat Majumder, Apurba Sarkar

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Oct. 28, 2024

Language: Английский

Citations

0
Enhanced Detection and Molecular Modeling of Adaptive Mutations in SARS-CoV-2 Coding and Non-Coding Regions Using the c/µ Test DOI Creative Commons
Nicholas J. Paradis, Chun Wu

Virus Evolution, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 1, 2024

Accurately identifying mutations under beneficial selection in viral genomes is crucial for understanding their molecular evolution and pathogenicity. Traditional methods like the Ka/Ks test, which assesses non-synonymous (Ka) versus synonymous (Ks) substitution rates, assume that substitutions at sites are neutral thus equal to mutation rate (µ). Yet, evidence suggests translated regions (TRs) untranslated (UTRs) can be strong (Ks > µ) strongly conserved ≈ 0), leading false predictions of adaptive from codon-by-codon analysis. Our previous work used a relative test (c/µ, c: UTR/TR, µ: rate) identify SARS-CoV-2 genome without neutrality assumption sites. This study refines c/µ by optimizing µ value, smaller set nucleotide amino acid both UTR (11 with 3) TR (69 nonsynonymous sites: 3 2.5; 107 Ks/µ 3). Encouragingly, top two 70% had reported or predicted effects literature. Molecular modeling some critical proteins (S, NSP11, NSP5) was carried out elucidate possible mechanism adaptivity.

Language: Английский

Citations

0