Betacoronavirus internal protein: role in immune evasion and viral pathogenesis

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

ABSTRACT Betacoronaviruses express a small internal (I) protein that is encoded by the same subgenomic RNA (sgRNA) as nucleocapsid (N) protein. Translation of +1 reading frame N sgRNA through leaky ribosomal scanning leads to expression I The an accessory reported evade host innate immune responses during coronavirus infection. Previous studies have shown proteins severe acute respiratory syndrome (SARS-CoV), SARS-CoV-2, and Middle East suppress type interferon production distinct mechanisms. In this review, we summarize current knowledge on betacoronaviruses from different subgenera, with emphasis its function role in pathogenesis.

Language: Английский

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SARS-CoV-2 and Coronaviruses: Understanding Transmission, Impact, and Strategies for Prevention and Treatment

Drugs and Drug Candidates, Journal Year: 2025, Volume and Issue: 4(1), P. 5 - 5

Published: Feb. 10, 2025

COVID-19, first identified in December 2019 Wuhan, China, is caused by the SARS-CoV-2 virus, a pathogen that primarily targets respiratory system and can lead to severe conditions such as acute distress syndrome (ARDS). Among seven coronaviruses known infect humans, three—SARS-CoV, MERS-CoV, SARS-CoV-2—are associated with illness significant morbidity. an enveloped, single-stranded RNA virus utilizes angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. The genetic sequence of highly mutable, leading emergence variants alter disease pathology transmission dynamics. World Health Organization (WHO) has classified these mutations into concern (VOCs), interest (VOIs), under monitoring (VUMs). This review provides in-depth analysis both historical emerging variants, summarizes recent advancements diagnostic methods detection, discusses current therapeutic strategies particular focus on virus-like particle (VLP) vaccines developed years. Additionally, we highlight ongoing approaches their implications managing COVID-19.

Language: Английский

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

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

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

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SARS-CoV-2 emerging Omicron subvariants with a special focus on BF.7 and XBB.1.5 recently posing fears of rising cases amid ongoing COVID-19 pandemic

Journal of Experimental Biology and Agricultural Sciences, Journal Year: 2022, Volume and Issue: 10(6), P. 1215 - 1221

Published: Dec. 31, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron versions have been the sole one circulating for quite some time. Subvariants BA.1, BA.2, BA.3, BA.4, and BA.5 of emerged over time through mutation, with BA.1 responsible most global pandemic between December 2021 January 2022. Other subvariants such as BQ.1, BQ.1.1, BA.4.6, BF.7, BA.2.75.2, XBB.1 appeared recently could cause a new wave increased cases amid ongoing COVID-19 pandemic. There is evidence that certain transmissibility, extra spike mutations, ability to overcome protective effects neutralizing antibodies immunological evasion. In recent months, BF.7 subvariant has in news due its spread China small number other countries, raising concerns about possible rebound cases. More recently, XBB.1.5 captured international attention an increase United States. As highly transmissible sublineage BA.5, well having shorter incubation potential reinfect or infect immune population, stronger infection ability. It appears regional landscape affected by amount timing previous waves, vaccination coverage, which turn determines whether escape sufficient drive waves. Expanding our understanding transmission efficacy vaccines, immunotherapeutics, antiviral drugs against newly emerging lineages, bolstering genomic facilities tracking their maintaining constant vigilance, shedding more light on evolution mutational events, would help development effective mitigation strategies. Importantly, reducing occurrence mutations recombination virus can be aided One health approach emphasizing significance combating zoonosis reversal linked COVID-19. This article provides brief overview variant, lineages subvairants special focus much infectious variations may once again threaten sharp globally currently pandemic, along presenting salient measures.

Language: Английский

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Chasing SARS-CoV-2 XBB.1.16 Recombinant Lineage in India and the Clinical Profile of XBB.1.16 cases in Maharashtra, India

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 26, 2023

ABSTRACT Background SARS-CoV-2 has evolved rapidly, resulting in emergence of lineages with competitive advantage over one another. Co-infections different can give rise to recombinant lineages. To date, XBB lineage is the most widespread worldwide, recently named XBB.1.16 causing a surge number COVID-19 cases India. Methodology The present study involved retrieval genome sequences from India (between 1 st December 2022 and 8 th April 2023) through GISAID; were curated, followed by phylogenetic analysis. Demographic clinical data Maharashtra, collected telephonically, recorded Microsoft® Excel, analysed using IBM® SPSS statistics, version 29.0.0.0 (241). Results A total 2,944 downloaded GISAID database, which 2,856 included following curation. dominated XBB.1.16* (36.17%) XBB.2.3* (12.11%) XBB.1.5* (10.36%). Of cases, 693 Maharashtra; 386 these study. features infection (XBB.1.16* 276 number) showed that 92% those had symptomatic disease, fever (67%), cough (42%), rhinorrhoea (33.7%), body ache (14.5%) fatigue (14.1%) being common symptoms. Presence comorbidity was found 17.7% cases. Among 91.7% vaccinated at least dose vaccine against COVID-19. While 74.3% home-isolated; 25.7% needed hospitalization/institutional quarantine, these, 33.8% oxygen therapy. Out seven (2.5%) succumbed disease. Majority who died belonged an elderly age group (60 years above), underlying comorbid condition/s, supplemental infected other co-circulating Omicron variants similar Conclusion reveals become predominant also shows outcome

Language: Английский

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Characterization of SARS-CoV-2 Variants in Military and Civilian Personnel of an Air Force Airport during Three Pandemic Waves in Italy

Microorganisms, Journal Year: 2023, Volume and Issue: 11(11), P. 2711 - 2711

Published: Nov. 5, 2023

We investigated SARS-CoV-2 variants circulating, from November 2020 to March 2022, among military and civilian personnel at an Air Force airport in Italy order classify viral isolates a potential hotspot for virus spread. Positive samples were subjected Next-Generation Sequencing (NGS) of the whole genome Sanger sequencing spike coding region. Phylogenetic analysis classified traced their evolutionary relationships. Clusters identified using 70% cut-off. methods yielded comparable results terms variant classification. In 2021, we several variants, including B.1.258 (4/67), B.1.177 (9/67), Alpha (B.1.1.7, 9/67), Gamma (P.1.1, 4/67), Delta (4/67). only Omicron its sub-lineage observed (37/67). screened detect naturally occurring resistance genomic regions, target new therapies, comparing them Wuhan Hu-1 reference strain. Interestingly, 2/30 non-Omicron carried G15S 3CLpro substitution responsible reduced susceptibility protease inhibitors. On other hand, unusual substitutions A1803V, D1809N, A949T on PLpro, D216N 3CLpro. Finally, P323L RdRp regions was not associated with mutational pattern related polymerase inhibitor resistance. This study highlights importance continuous surveillance monitor evolution general population, as well restricted communities.

Language: Английский

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Association of SARS-CoV-2 Nucleocapsid Protein Mutations with Patient Demographic and Clinical Characteristics during the Delta and Omicron Waves

Microorganisms, Journal Year: 2023, Volume and Issue: 11(5), P. 1288 - 1288

Published: May 15, 2023

SARS-CoV-2 genomic mutations outside the spike protein that may increase transmissibility and disease severity have not been well characterized. This study identified in nucleocapsid their possible association with patient characteristics. We analyzed 695 samples from patients confirmed COVID-19 Saudi Arabia between 1 April 2021, 30 2022. Nucleocapsid were through whole genome sequencing. 𝜒2 tests t assessed associations Logistic regression estimated risk of intensive care unit (ICU) admission or death. Of 60 identified, R203K was most common, followed by G204R, P13L, E31del, R32del, S33del. These associated reduced ICU admission. S33del also By contrast, D63G, R203M, D377Y increased Most detected SR-rich region, which low The C-tail central linker regions admission, whereas N-arm region risk. Consequently, N must be observed, as they exacerbate viral infection severity. Additional research is needed to validate mutations' clinical outcomes.

Language: Английский

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Genomic Surveillance and Mutation Analysis of SARS-CoV-2 Variants among Patients in Saudi Arabia

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

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Infection-Simulator, Immunostimulatory and Immunomodulatory Effects of Interferons I and III in Biological Systems: A New Era in Vaccinology and Therapeutics Possible?

Published: July 10, 2024

The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses prevalent alpha/ beta coronaviruses, but also Middle East Respiratory Syndrome (MERS-CoV) SARS-CoV-1, recent SARS–CoV–2 variants, increasing demands for effective immunogens therapeutic approaches that will reduce global burden further from SARS–CoV-2 affected individuals may experience post sequelae (PASC) or “Long COVID”. Following a worldwide programme prophylactic vaccination, there is still dilemma in efforts to find early would treat novel SARS-CoV-2 variants prevent future epidemics pandemics within host human animal populations, where zoonotic cross species transfer naturally occurs. Concerns about viral immune escape intersect at specific point; gained evolutionary ability several viruses co–infect compete against previous scientific advances since 1796 remain undetected asymptomatic during stages progressing symptomatic via double methylation 5' end eukaryotic DNA RNA-based genomes, 7-MeGpppA2’-O-Me cap, its capping process performed by activated 2’ - O Methyltransferase (MTase) enzyme, complex two non-structural proteins (NSPs) joined together through an activation (NSP10/16) N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered polymorphic translate NSP1, prevents various Pattern Recognition Receptors (PRRs), consequently, detection Pathogen-Associated Molecular Patterns (PAMPs) Damage-Associated (DAMPs) alike. NSP1 silences important interferon-encoding genes (INGs) interferon-stimulated (ISGs), signalled paracrine manner neighbouring cells, induces apoptosis inducing effect “trace erase” making as immunologically “invisible” possible initial, key replication distribution, all such mechanisms occurring independently cause. Another NSP NSP14, plays functional roles are independent each other; produce new genetic material purpose maintaining validity genome well, not just methyl group 5’ genome. Other NSPs share role 10, 14 16 directly suppressing PRRs ISGs, help virus self-camouflaging first- second-line immunity, thereby often severely impacting quality produced adaptive responses. outcome phenomena sharp decrease Type I III interferons' (IFNs) rate synthesis usually occur affect homeostatic cellular pathways, resulting induced apoptosis. Nonetheless, effects microbial evasion development carcinogenic pathologies widely known. In short, developed proportionate response responses, relying on gaps mostly situated natural system their molecular self-camouflaging. Scientists numerous treatment generally showed good success rates fewer risks adverse events, present COVID-19 research should be taken into consideration whilst filtering most appropriate solutions. For example, administration recombinant interferons nasal mucosa layer, mediators anti–viral activity, can simulate intracellular stimulate activity timely manner, training innate cells develop appropriately adequate B T cells. example could involve lymphocytes low dose IFNs possibly III, insertion lymphatic system, alongside additional recruitment plasmacytoid dendritic (pDCs) interferon “factories”, management. It might focusing offering information genetics protein structure pathogen, rather than first-line faster, excessively increases specificity, reach level brings opportunity evolve previously-developed mechanisms. until community realises this potentially crucial aspect large proportions world population probably continue face serious diseases over coming decades, evidenced dengue fever more recently, monkeypox avian flu. Of note, been indicated IFN / display significant immunising, clinical onset-attenuating many evoked diseases, well number oncological diseases.

Language: Английский

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SARS-CoV-2 and its impact on the cardiovascular and digestive systems – The interplay between new virus variants and human cells

Computational and Structural Biotechnology Journal, Journal Year: 2023, Volume and Issue: 21, P. 1022 - 1029

Published: Jan. 1, 2023

Since infection with the novel coronavirus SARS-CoV-2 first emerged in Wuhan, China, December 2019, world has been battling pandemic COVID-19. Patients of all ages and genders are now becoming infected new variant (Omicron) worldwide, its subvariants continue to pose a threat health life. This article provides literature review cardiovascular gastrointestinal complications resulting from infection. COVID-19 primarily caused respiratory symptoms, but can affect many vital organs. binds human cell receptor (angiotensin-converting enzyme 2 – ACE2) that is predominantly expressed heart tract, which why we focused on these high transmissibility Omicron ability evade immune system have raised worldwide concern, tried summarise current knowledge about development structural point view highlight differences binding receptors proteases compared previous VOC.

Language: Английский

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