SARS-CoV-2 spike protein in infectivity

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 21 - 56

Published: Jan. 1, 2025

Language: Английский

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Epimaps of the SARS-CoV-2 Receptor-Binding Domain Mutational Landscape: Insights into Protein Stability, Epitope Prediction, and Antibody Binding

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 301 - 301

Published: Feb. 18, 2025

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses an ongoing threat to the efficacy vaccines and therapeutic antibodies. Mutations predominantly affect receptor-binding domain (RBD) spike protein, which mediates viral entry. RBD is also a major target monoclonal antibodies that were authorised for use during pandemic. In this study, in silico approach was used investigate mutational landscape SARS-CoV-2 variants, including currently circulating Omicron subvariants. A total 40 single-point mutations assessed their potential effect on protein stability dynamics. Destabilising effects predicted such as L455S F456L, while stabilising R346T. Conformational B-cell epitope predictions subsequently performed wild-type (WT) variant RBDs. from located within residues regions found correspond sites targeted by Furthermore, homology models generated utilised protein-antibody docking. binding characteristics 10 against WT 14 evaluated. Through evaluating affinities, interactions, energy contributions residues, contributing evasion identified. findings study provide insight into structural molecular mechanisms underlying neutralising antibody evasion. Future development could focus broadly antibodies, engineering with enhanced affinity, targeting beyond RBD.

Language: Английский

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Potent bivalent nanobody constructs that protect against the SARS-CoV-2 XBB variant

npj Viruses, Journal Year: 2025, Volume and Issue: 3(1)

Published: March 13, 2025

Most antibody-based therapeutics approved for SARS-CoV-2 treatment have shown greatly reduced neutralization activity against emerging Omicron variants. To target recent variants, we developed XBB-specific antibody-like by screening a yeast surface-displayed single-domain antibody library the receptor binding domain of XBB spike protein. Three lead nanobodies, XNb 4.13, 4.14, and 4.15, were selected based on their affinity to protein fused mouse Fc domain. While all three constructs showed sub-nanomolar affinities S protein, 4.13-Fc 4.14-Fc also neutralized in vitro. Intraperitoneal injection intranasal delivery protected transgenic mice from challenge with virus significant reduction viral lung titers post-infection. These identified using surface display potential as that can protect

Language: Английский

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The Virus Entry Pathway Determines Sensitivity to the Antiviral Peptide TAT-I24

Viruses, Journal Year: 2025, Volume and Issue: 17(4), P. 458 - 458

Published: March 23, 2025

The peptide TAT-I24, a fusion of the TAT (amino acids 48–60) and 9-mer I24, has been previously shown to neutralize several double-stranded (ds) DNA viruses in vitro. We have now extended testing potentially sensitive RNA analyzed antiviral effect against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). In Vero E6 cells, TAT-I24 neutralized human 2019-nCoV isolate (Wuhan variant) dose-dependent manner, while it was unable two SARS-CoV-2 variants concern, Delta Omicron. Moreover, could not significantly any lung carcinoma cell line Calu-3, which provides an alternative entry route for by direct membrane fusion. Therefore, possible dependence on virus uptake endocytosis investigated exposing cells chloroquine (CQ), inhibitor endosomal acidification. Wuhan variant highly inhibition CQ, further enhanced less higher concentrations CQ compared variant. microscopic analysis COS-7 using rhodamine-labeled (Rho-TAT-I24) showed localization fluorescent co-localization with transfected GFP-Rab14 but GFP-Rab5. As these proteins are found distinct pathways, our results indicate that pathway determines sensitivity peptide.

Language: Английский

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In-silico analysis of Spike and envelope protein mutations in Omicron variants from Indonesia and high-case countries

Asia-Pacific Journal of Molecular Biology and Biotechnology, Journal Year: 2025, Volume and Issue: unknown, P. 77 - 86

Published: March 31, 2025

Coronaviruses have an envelope made up of four main structural proteins, namely Spike protein that has a major role in binding and tends to undergo mutations. The purpose this study was analyze mutations occur the nucleotide sequence Indonesian Omicron variant protein, which will be compared with results analysis from 5 countries highest cases. began search for gene coding SARS-CoV-2 had patient isolates on Global Initiative Sharing All Influenza Data (GISAID) website. obtained then analyzed determine location sample showed composition lead decreased stability (11 mutations), 2 neutral cause increased (4 mutations). Mutations namely, G339D, K417N, N440K, T478K, E484A, Q498R, Y505H, D405N, R408S, L452R, F486V, all disease. reduce are S371L, G446S, Q493R, G496S, each mutation causing increase virulence. S373P, S375F, N501Y. three led Indonesia higher virulence other variants countries.

Language: Английский

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Overview of SARS-CoV-2 variants in the federation of Bosnia and Herzegovina throughout four waves of the pandemic

Technology and Health Care, Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Aim COVID-19 pandemic, caused by SARS-CoV-2, has had a profound impact on global health, including in Bosnia and Herzegovina, which faced unique challenges due to limited testing high mortality rates. This analysis aimed identify mutations detect different SARS-CoV-2 lineages across four pandemic waves. Methodology A total of 127 samples were collected sequenced from patients the Federation providing comprehensive overview viral genetic diversity this region. Two sequencing platforms, Ion Torrent Illumina, used, whereby 37 platform, while others Illumina platform. Results study presents genomic variants circulating Herzegovina over distinct waves, spanning March 2020 April 2023. Examination variations these waves revealed key associated with transmission potential virulence. Conclusion These insights into evolution emphasizes importance continuous surveillance understand strengthen public health responses future pandemics.

Language: Английский

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Role of Dengue in SARS-CoV-2 Evolution in Dengue Endemic Regions

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Abstract Evidence suggests that dengue virus (DV) antibodies (Abs) and SARS-CoV-2 Abs were cross-reactive, resulting in reciprocal serological cross-interaction providing cross-protection populations co-endemic regions. It became apparent from the present study variants preferentially selecting mutation(s)/deletions spike to evade interaction with DV Abs. We looked at mutations protein how they affected antigenicity, focusing on successively emergent major such as B.1.1.7 (Kent), B.1.617 (Delta), B.1.617.2.1 (Delta-Plus), B.1.1.529 (Omicron-BA.1) (Omicron-BA.2). To further understand effect of cross-reactive mutation(s), structural studies docking simulations performed using DV-2 envelope (E) Signature mutation (s) implied majority above changes driven by rather than immune pressure (preceding variants). This was supported fact lately like Omicrons (2022-23) least 50% less compared preceding predominant strains. observed cross-binding pre-pandemic Ab-positive serums synthetic peptides ELISA, designed certain regions RBD which showed maximum cross-interactions E

Language: Английский

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Cases of BA.2.75 and recent BA.2.75.2 subvariant of Omicron are increasing in India: Is it alarming at the global level?

Annals of Medicine and Surgery, Journal Year: 2022, Volume and Issue: 84

Published: Nov. 18, 2022

Dear Editor Scientists have noted several variants of SARS-CoV-2 during the pandemic's last two and half years. Ongoing random mutations in generated these variants. The World Health Organization (WHO) provided naming using Greek alphabets along with existing Pango nomenclature for (a dynamic virus lineage). Some examples are B.1.1.7 variant as Alpha (α), B.1.351 Beta (β), B.1.617.2 Delta (δ), P.1 Gamma (γ), etc. It has been noticed that had created a surge COVID-19 cases country origin then rapidly transmitted to different countries [1,2]. However, among variants, some extensively variant, Omicron, is observed highly variant. Omicron first emerged South Africa. was identified November 2021. WHO intimated about this new on 24, 2021 [3]. After identifying it high transmission capacity well ability overpower vaccine induced protective immunity antibodies-based therapies via immune escape mechanisms. Due rate, labeled concern (VOC) within days [4]. Subsequently, now spread 150 countries. Along numerous genome [5,6]. Approximately 50 revealed throughout Omicron. At same time, recorded hotspot ‘S’ protein. spike protein harbors approx. 32 sequence [6]. About 26 RBD (receptor binding domain) part [7]. Analysis sequences from ongoing mutating process sublineages or subvariants time time. From surveillance studies more than one hundred subvariant reported be Among them, emerging BA.1, BA.2, BA.4 BA.5 [8,9]. BA.2 June 2022 European that, were BA.2. BA.2.74, BA.2.75, BA.2.76, [10]. BA.2.75 BA.2.12.1 significant (Fig. 1a).Fig. 1.: origin, distribution, frequencies, (a) A schematic diagram shows evolution BA.2.75.1 (b) map distribution (c) frequencies BA.2.75. indicated started increase May 2020 (d) S-protein Fig.1b 1c developed Nextstrain server.Fig. ContinuedFig. ContinuedPresently, 20 worldwide. Suddenly, scientists quickly rising India. Although presently low other compared India, however, alarmed regarding possible risk rise instances. number falling remarkably many Nevertheless, hospitalization due infection found maximum samples India contain subvariant. assuming will keep growing globally, mainly Asia [11]. specimen collected January 7, presence 1a) [12]. Afterwards, countries, gradual May–June 1c). like USA, Canada, UK, Singapore, Japan properties characterized by quite few scientists. In simulation study, Zappa et al. showed 57-fold increased receptor affinity (ACE2 receptor). also markedly higher (more 3000-fold) (B.1.1.7) [13]. Shaheen defined mutations: R493Q, G446S, W152R, K147E. They R493Q G446S alarming mutations. mutation might role resistance ACE2 Recently, Sheward illustrated nine additional which N460K, G339H, G257S, I210V, F157L, K147E 1d). shown neutralizing antibodies (nAbs). stated responsible nAbs phenomena elicited current vaccines. Furthermore, site evasion LY-CoV140 antibody (bebtelovimab). decrease potentiality against reported. potency cilgavimab reduced 11-fold B.1 (D614G). unable neutralize Such etesevimab, bamlanivimab, imdevimab, casivirimab. minor reduction bebtelovimab, retains sensitivity show moderate susceptibility subvariant, tixagevimab [14]. recently further forming called BA.2.75.2 1a). currently local news agencies said newer very [15]. transmissible others trying establish dominant there no scientific report published till date direction. present eight including Chile, England, Spain Germany Global tracking immediately required earlier replaced subvariants, rather comparatively transmissible, therefore could pose chances worldwide rapidly. Of note, research needed understand newly should unfold features transmission, susceptibility, pattern, affinity, BA.2.75.2. necessary develop proper diagnostics confirmatory detection We urge study direction solve enhance its monitoring activities. This help us fight contagious feasibly evasive formulating proactive control measures preparedness plans avoiding any wave infections, save humanity amid pandemic. Researchers anticipated coming would pave ways pandemic linger far into future. Under such scenario, available vaccines become less potent render thus need updated. next generation proof counteract evolving subvariants. Ethical approval No applicable. Sources funding fund received. Author contribution Chiranjib Chakraborty: Conceptualization, Data Curation, Investigation, Writing - Original Draft, review & editing. Manojit Bhattacharya: Validation figure development. Kuldeep Dhama: Validation; editing-reviewing. All authors critically reviewed approved final version manuscript. Trial register Name registry: Not applicable Unique Identifying registration ID: Hyperlink your specific (must publicly accessible checked): Guarantor Professor Chakraborty, Department Biotechnology, School Life Science Adamas University, Kolkata, West Bengal 700126, Email: [email protected] Tel: +91-9871608125 Consent Provenance peer commissioned, internally peer-reviewed. statement data correspondence article not sensitive nature public domain. confidential nature. Declaration competing interest conflicts relevant article. Acknowledgements thankful their respective institutes universities. Chakraborty Bhattacharya Dhama 1Department Bengal, 2Department Zoology, Fakir Mohan Vyasa Vihar, Balasore, 756020, Odisha, 3Division Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, Uttar Pradesh, E-mail addresses:[email protected];

Language: Английский

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Antibody evasion associated with the RBD significant mutations in several emerging SARS-CoV-2 variants and its subvariants

Drug Resistance Updates, Journal Year: 2023, Volume and Issue: 71, P. 101008 - 101008

Published: Sept. 22, 2023

Language: Английский

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COVID-19 genome surveillance: A geographical landscape and mutational mapping of SARS-CoV-2 variants in central India over two years

Virus Research, Journal Year: 2024, Volume and Issue: 344, P. 199365 - 199365

Published: March 29, 2024

Reading the viral genome through whole sequencing (WGS) enables detection of changes in genome. The rapid SARS-CoV-2 may cause immune escape leading to an increase pathogenicity or infectivity. Monitoring mutations genomic surveillance helps understand amino acid resulting from mutation. These changes, especially spike glycoprotein, have implications on virus by rendering it immune-escape. region Vidarbha Maharashtra represents 31.6 % state's total area. It holds 21.3 population. In total, 7457 positive samples belonging 16 Indian States were included study, out which 3002 passed quality control criteria. metadata study was sourced Integrated Health Information Platform (IHIP). sequenced samples, including FASTA sequence, submitted Global Initiative Sharing Avian Influenza Data (GISAID) and biological data centre (IBDC). This identified 104 different pango-lineages classified into 19 clades. We also analysed mutation profiles variants found showed eight interest, L18F, K417N, K417T, L452R, S477N, N501Y, P681H, P681R, concern E484K glycoprotein region. November 2020 December 2022, making this most comprehensive conducted for

Language: Английский

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