SARS-CoV-2 nsp1 mediates broad inhibition of translation in mammals

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115696 - 115696

Published: May 1, 2025

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 1 (nsp1) promotes innate immune evasion by inhibiting host translation in human cells. However, the role of nsp1 other species remains elusive, especially bats-natural reservoirs sarbecoviruses with a markedly different system than humans. We reveal that potently inhibits Rhinolophus lepidus bat cells, which belong to same genus as known sarbecovirus reservoir hosts. determined cryoelectron microscopy structure bound R. 40S ribosomal subunit, showing it blocks mRNA entry channel targeting highly conserved site among mammals. Accordingly, we found blocked mammalian cells from several species, underscoring its broadly inhibitory activity and numerous SARS-CoV-2 Our findings illuminate arms race between coronaviruses immunity, providing foundation for understanding determinants viral maintenance hosts spillover.

Language: Английский

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Nsp1 stalls DNA polymerase α at DNA hairpins

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 21, 2025

The human primosome, a four-subunit complex of DNA primase and polymerase alpha (Polα), plays critical role in replication by initiating RNA synthesis on both chromosome strands. A recent study has shown that major virulence factor the SARS-CoV-2 infection, Nsp1 (non-structural protein 1), forms stable with Polα but does not affect primosome activity. Here we show inhibits across inverted repeats prone to hairpin formation. Analysis current structural data revealed overlapping binding sites for winged helix-turn-helix domain RPA (wHTH) Polα, pointing potential competition between them. Comparison inhibitory effect wHTH bypass showed an eightfold lower IC50 value (1 µM). This provides valuable insight into mechanism inhibition during infection.

Language: Английский

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The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development—A Systematic Review

Viruses, Journal Year: 2022, Volume and Issue: 14(5), P. 991 - 991

Published: May 7, 2022

Live-attenuated SARS-CoV-2 vaccines received relatively little attention during the COVID-19 pandemic. Despite this, several methods of obtaining attenuated coronaviruses are known. In this systematic review, strategies coronavirus attenuation, which may potentially be applied to SARS-CoV-2, were identified. PubMed, Scopus, Web Science and Embase databases searched identify relevant articles describing attenuating mutations tested in vivo. case other than sequence alignment was used exclude that cannot SARS-CoV-2. Potential immunogenicity, safety efficacy vaccine discussed based on animal studies data. A total 27 attenuation strategies, create 101 different coronaviruses, have been described 56 eligible articles. The disruption furin cleavage site spike protein identified as most promising strategy. replacement core sequences transcriptional regulatory signals, prevents recombination with wild-type viruses, also appears particularly advantageous. Other important encompassed mostly prevention evasion innate immunity. Sufficiently typically caused no meaningful disease susceptible animals protected them from challenges virulent virus. This indicates considered a potential strategy fight threat posed by

Language: Английский

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Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8122 - 8122

Published: July 23, 2022

The relentless, protracted evolution of the SARS-CoV-2 virus imposes tremendous pressure on herd immunity and demands versatile adaptations by human host genome to counter transcriptomic epitranscriptomic alterations associated with a wide range short- long-term manifestations during acute infection post-acute recovery, respectively. To promote viral replication active persistence, envelope protein regulates cell microenvironment including pH ion concentrations maintain high oxidative environment that supports template switching, causing extensive mitochondrial damage activation pro-inflammatory cytokine signaling cascades. Oxidative stress distress induce dynamic changes both RNA m

Language: Английский

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Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders

Viruses, Journal Year: 2022, Volume and Issue: 14(10), P. 2270 - 2270

Published: Oct. 16, 2022

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 ten three by exploring two pathological mechanisms: (i) dysregulation host biological processes via virus–host protein–protein interactions (PPIs), (ii) autoreactivity severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes “self” proteins molecular mimicry. We also identify potential genetic risk factors which in combination SARS-CoV-2 infection might lead disease development. Our analysis indicated that neurodegenerative (NDs) have a higher number disease-associated can be modulated PPIs than disorders. The sequence similarity presence several matching 5-mer and/or 6-mer linear motifs autoreactive found Alzheimer’s (AD), Parkinson’s (PD), Myasthenia Gravis (MG) Multiple Sclerosis (MS). results include recognize amyloid-beta precursor protein (APP), microtubule-associated tau (MAPT), acetylcholine receptors, glial fibrillary acidic (GFAP), neurofilament light polypeptide (NfL) major myelin proteins. Altogether, our suggest there an for NDs both PPIs.

Language: Английский

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