Two sides of the same coin: the N-terminal and the receptor-binding domains of SARS-CoV-2 Spike

Future Virology, Год журнала: 2023, Номер 18(2), С. 75 - 78

Опубликована: Фев. 1, 2023

Tweetable abstract The SARS-CoV-2 Spike receptor binding domain and N-terminal interact with each other in an intricate mechanism. Mutations modulate the interplay between host molecules. This editorial comments on intricacies of interactions.

Язык: Английский

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Adaptive advantage of deletion repair in the N-terminal domain of the SARS-CoV-2 spike protein in variants of concern

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 24, 2024

Abstract Mutations within the N-terminal domain (NTD) of spike (S) protein are critical for emergence successful SARS-CoV-2 viral lineages. The NTD has been repeatedly impacted by deletions, often exhibiting complex and dynamic patterns, such as recurrent disappearance deletions in dominant variants. This study investigates influence repair lineage-defining found BA.1 lineage (Omicron variant) on success. We performed comparative genomic analyses more than 10 million genomes from GISAID to decipher transmission success viruses lacking S:ΔH69/V70, S:ΔV143/Y145, or both. These findings were contrasted against a screening publicly available raw sequencing data, revealing substantial discrepancies between data repositories, suggesting that spurious deletion observations may result systematic artifacts. Specifically, events approximately an order magnitude less frequent read-run survey. Our results suggest rare, isolated with limited direct evolution transmission. Nevertheless, could facilitate fitness-enhancing mutations. To explore potential drivers we characterized phenotype markers surrogate vitro system. Repair S:ΔH69/V70 reduced infectivity, while simultaneous S:ΔV143/Y145 led lower fusogenicity. In contrast, individual enhanced both fusogenicity susceptibility neutralization sera vaccinated individuals. work underscores genotype-phenotype landscape SARS-CoV-2, which impacts biology, efficiency, immune escape potential, offering insights relevance public health, surveillance, adaptive mechanisms driving emerging

Язык: Английский

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Emergence of SARS-CoV-2 omicron variant JN.1 in Tamil Nadu, India - Clinical characteristics and novel mutations

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 30, 2024

In December 2023, we observed a notable shift in the COVID-19 landscape, when JN.1 omicron emerged as predominant SARS-CoV-2 variant with 95% incidence. We characterized clinical profile, and genetic changes JN.1, an emerging of interest. Whole genome sequencing was performed on positive specimens, followed by sequence analysis. Mutations within spike protein sequences were analysed compared previously reported lineages sub-lineages, to identify potential impact unique mutations structure possible alterations functionality. Several dynamic identified herein. Molecular docking analysis showed binding affinity, key interacting residues wild-type mutated structures host cell receptors entry viz., ACE2, CD147, CD209L AXL. Our data provides insights emergence newer variants highlights necessity for robust sustained global genomic surveillance SARS-CoV-2.

Язык: Английский

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Convergence of immune escape strategies highlights plasticity of SARS-CoV-2 spike

PLoS Pathogens, Год журнала: 2023, Номер 19(5), С. e1011308 - e1011308

Опубликована: Май 1, 2023

The global spread of the SARS-CoV-2 virus has resulted in emergence lineages which impact effectiveness immunotherapies and vaccines that are based on early Wuhan isolate. All currently approved employ spike protein S, as it is target for neutralizing antibodies. Here we describe two isolates with unusually large deletions N-terminal domain (NTD) spike. Cryo-EM structural analysis shows result complete reshaping NTD supersite, an antigenically important region NTD. For both variants remodeling negatively affects binding all tested NTD-specific antibodies outside supersite. one variants, observed a P9L mediated shift signal peptide cleavage site resulting loss disulfide-bridge; unique escape mechanism high antigenic impact. Although disulfide mutations rare, similar modifications have become independently established several other lineages, indicating possibility to more dominant future. plasticity foreshadows its broad potential immune continued SARS-CoV-2.

Язык: Английский

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Enhancement of SARS-CoV-2 Infection via Crosslinking of Adjacent Spike Proteins by N-Terminal Domain-Targeting Antibodies

Viruses, Год журнала: 2023, Номер 15(12), С. 2421 - 2421

Опубликована: Дек. 13, 2023

The entry of SARS-CoV-2 into host cells is mediated by the interaction between spike receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2). Certain human antibodies, which target N-terminal (NTD) at a distant epitope from cell binding surface, have been found to augment ACE2 enhance infection. Notably, these antibodies exert their effect independently antibody fragment crystallizable (Fc) region, distinguishing mode action previously described antibody-dependent infection-enhancing (ADE) mechanisms. Building upon previous hypotheses experimental evidence, we propose that NTD-targeting (NIEAs) achieve through crosslinking neighboring proteins. In this study, present refined structural models NIEA antigen-binding region (Fab)–NTD complexes, supported molecular dynamics simulations hydrogen–deuterium exchange mass spectrometry (HDX-MS). Furthermore, provide direct evidence confirming NTDs NIEAs. Collectively, our findings advance understanding mechanisms underlying NIEAs impact on

Язык: Английский

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