SARS-CoV-2 Nsp1 regulates translation start site fidelity to promote infection DOI Creative Commons
Ranen Aviner, Peter V. Lidsky, Yinghong Xiao

et al.

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

Published: July 7, 2023

A better mechanistic understanding of virus-host interactions can help reveal vulnerabilities and identify opportunities for therapeutic interventions. Of particular interest are essential that enable production viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses reporter assays to detect changes polysome composition protein synthesis during SARS-CoV-2 (CoV2) infection. We specific translation factors molecular chaperones whose inhibition impairs infectious particle without major toxicity host. find CoV2 non-structural Nsp1 selectively enhances through functional with initiation factor EIF1A. When EIF1A is depleted, more ribosomes initiate from upstream CUG start codon, inhibiting genes reducing titers. Together, our work describes multiple dependencies on host biosynthetic networks identifies druggable targets potential antiviral development.

Language: Английский

SARS-CoV-2 biology and host interactions DOI
Silvio Steiner, Annika Kratzel, G. Tuba Barut

et al.

Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(4), P. 206 - 225

Published: Jan. 15, 2024

Language: Английский

Citations

85
Universal features of Nsp1-mediated translational shutdown by coronaviruses DOI Creative Commons
Katharina Schubert, Evangelos D. Karousis,

Ivo Ban

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(19), P. 3546 - 3557.e8

Published: Oct. 1, 2023

Language: Английский

Citations

25
A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories DOI Creative Commons
Audrey L. Heffner, Tracey A. Rouault

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 256 - 256

Published: Feb. 13, 2025

In 2021, at the height of COVID-19 pandemic, coronavirus research spiked, with over 83,000 original articles related to word "coronavirus" added online resource PubMed. Just 2 years later, in 2023, only 30,900 were added. While, irrefutably, funding drastically decreased, a possible explanation for decrease interest is that projects on SARS-CoV-2, causative agent COVID-19, halted due challenge establishing good cellular or animal model system. Most laboratories do not have capabilities culture SARS-CoV-2 'in house' as this requires Biosafety Level (BSL) 3 laboratory. Until recently, BSL laboratory endemic coronaviruses was arduous low cytopathic effect isolated cell infection models and lack means quantify viral loads. The purpose review article compare human provide an assessment latest techniques use coronaviruses-HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1-as lower-biosafety-risk more pathogenic coronaviruses-SARS-CoV-2, SARS-CoV, MERS-CoV.

Language: Английский

Citations

1
Cap-independent translation and a precisely located RNA sequence enable SARS-CoV-2 to control host translation and escape anti-viral response DOI Creative Commons
Boris Slobodin, Urmila Sehrawat, Anastasia I. Lev

et al.

Nucleic Acids Research, Journal Year: 2022, Volume and Issue: 50(14), P. 8080 - 8092

Published: July 18, 2022

Translation of SARS-CoV-2-encoded mRNAs by the host ribosomes is essential for its propagation. Following infection, early expressed viral protein NSP1 binds ribosome, represses translation, and induces mRNA degradation, while elicits an anti-viral response. The mechanisms enabling to escape this multifaceted repression remain obscure. Here we show that expression leads destabilization multi-exon cellular mRNAs, intron-less transcripts, such as interferon genes, relatively stable. We identified a conserved precisely located cap-proximal RNA element devoid guanosines confers resistance NSP1-mediated translation inhibition. Importantly, primary sequence rather than secondary structure critical protection. further genomic 5'UTR SARS-CoV-2 drives cap-independent promotes in eIF4E-independent Torin1-resistant manner. Upon expression, enhances translation. However, sub-genomic 5'UTRs are highly sensitive eIF4E availability, rendering propagation partially Torin1. conclude combined degradation spliced inhibition single-exon along with unique features present 5'UTRs, ensure robust mRNAs. These can be exploited potential therapeutic targets.

Language: Английский

Citations

33
Nsp1 proteins of human coronaviruses HCoV-OC43 and SARS-CoV2 inhibit stress granule formation DOI Creative Commons
Stacia M. Dolliver, Mariel Kleer, Maxwell P. Bui-Marinos

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(12), P. e1011041 - e1011041

Published: Dec. 19, 2022

Stress granules (SGs) are cytoplasmic condensates that often form as part of the cellular antiviral response. Despite growing interest in understanding interplay between SGs and other biological viral replication, role SG formation during coronavirus infection remains poorly understood. Several proteins from different coronaviruses have been shown to suppress upon overexpression, but there only a handful studies analyzing coronavirus-infected cells. To better understand inhibition by coronaviruses, we analyzed with human common cold OC43 (HCoV-OC43) pandemic SARS-CoV2. We did not observe induction infected cells both viruses inhibited eukaryotic translation initiation factor 2α (eIF2α) phosphorylation induced exogenous stress. Furthermore, SARS-CoV2 observed sharp decrease levels SG-nucleating protein G3BP1. Ectopic overexpression nucleocapsid (N) non-structural 1 (Nsp1) HCoV-OC43 formation. The Nsp1 arsenite-induced eIF2α phosphorylation, alone was sufficient cause G3BP1 levels. This phenotype dependent on depletion mRNA mediated associated nuclear accumulation TIAR. test overexpressing EGFP-tagged significant virus replication compared control expressing EGFP. existence multiple suppression mechanisms conserved suggest may represent an important host defense target ensure efficient replication.

Language: Английский

Citations

31
Targeting SARS-CoV-2 Non-Structural Proteins DOI Open Access
W.G. Tam, Ana C. Lorenzo‐Leal, Luis R. Hernández

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 13002 - 13002

Published: Aug. 20, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped β that causes disease (COVID-19), leading to a deadly pandemic has claimed millions of lives worldwide. Like other coronaviruses, the SARS-CoV-2 genome also codes for non-structural proteins (NSPs). These NSPs are found within open reading frame 1a (ORF1a) and 1ab (ORF1ab) encode NSP1 NSP11 NSP12 NSP16, respectively. This study aimed collect available literature regarding NSP inhibitors. In addition, we searched natural product database looking similar structures. The results showed structures could be tested as potential inhibitors NSPs.

Language: Английский

Citations

22
Coronavirus takeover of host cell translation and intracellular antiviral response: a molecular perspective DOI Creative Commons
Evangelos D. Karousis, Katharina Schubert, Nenad Ban

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(2), P. 151 - 167

Published: Jan. 10, 2024

Coronaviruses are a group of related RNA viruses that cause respiratory diseases in humans and animals. Understanding the mechanisms translation regulation during coronaviral infections is critical for developing antiviral therapies preventing viral spread. Translation single-stranded genome host cell cytoplasm an essential step life cycle coronaviruses, which affects cellular mRNA landscape many ways. Here we discuss various strategies control, including how members Betacoronavirus genus shut down suppress innate immune functions, as well role non-structural protein 1 (Nsp1) process. We also outline fate RNA, considering stress response triggered infected cells, describe unique features contribute to programmed ribosomal -1 frameshifting, editing, shutdown evasion.

Language: Английский

Citations

8
Antiviral responses versus virus-induced cellular shutoff: a game of thrones between influenza A virus NS1 and SARS-CoV-2 Nsp1 DOI Creative Commons
Ahmed Magdy Khalil, Aitor Nogales, Luis Martínez‐Sobrido

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 5, 2024

Following virus recognition of host cell receptors and viral particle/genome internalization, viruses replicate in the via hijacking essential machinery components to evade provoked antiviral innate immunity against invading pathogen. Respiratory infections are usually acute with ability activate pattern (PRRs) in/on cells, resulting production release interferons (IFNs), proinflammatory cytokines, chemokines, IFN-stimulated genes (ISGs) reduce fitness mitigate infection. Nevertheless, game between is a complicated dynamic process, which they restrict each other specific factors maintain their own advantages win this game. The primary role non-structural protein 1 (NS1 Nsp1) influenza A (IAV) pandemic severe respiratory syndrome coronavirus 2 (SARS-CoV-2), respectively, control host-induced immune responses. This review provides comprehensive overview genesis, spatial structure, cellular interactors, mechanisms underlying unique biological functions IAV NS1 SARS-CoV-2 Nsp1 infected cells. We also highlight both proteins modulating replication pathogenicity. Eventually, because important during infection, we describe promising potential as targets for therapy development live attenuated vaccines (LAV). Conclusively, play an virus–host interactions, replication, pathogenesis, pave way develop novel prophylactic and/or therapeutic interventions treatment these human pathogens.

Language: Английский

Citations

6
SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA DOI Creative Commons
Ranen Aviner, Peter V. Lidsky, Yinghong Xiao

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1011535 - e1011535

Published: Feb. 9, 2024

A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses reporter assays to detect changes protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We specific translation factors molecular chaperones used by CoV2 promote maturation its own proteins. These be targeted inhibit infection, without major toxicity host. also find non-structural 1 (Nsp1) cooperates with initiation EIF1 1A selectively enhance RNA. When EIF1/1A depleted, more ribosomes initiate from a conserved upstream CUG start codon found all genomic subgenomic RNAs. This results higher open reading frame (uORF1) lower main ORF, altering stoichiometry proteins attenuating Replacing AUG strongly inhibits ORF independently Nsp1, EIF1, or EIF1A. Taken together, our work describes multiple on host biosynthetic networks proposes model dosage control through Nsp1-mediated site selection.

Language: Английский

Citations

6
Evolution and Impact of Nucleic Acid Amplification Test (NAAT) for Diagnosis of Coronavirus Disease DOI Creative Commons

Sumbul Fatma Khan,

Priyanka Rathod, Vivek Kumar Gupta

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(20), P. 8124 - 8146

Published: April 30, 2024

ADVERTISEMENT RETURN TO ARTICLES ASAPReviewNEXTEvolution and Impact of Nucleic Acid Amplification Test (NAAT) for Diagnosis Coronavirus DiseaseSumbul Fatma KhanSumbul KhanDepartment Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, 440033, MS IndiaMore by Sumbul KhanView BiographyView Biography, Priyanka RathodPriyanka RathodDepartment Rathod, Vivek K. GuptaVivek GuptaDepartment Biochemistry, National JALMA Institute Leprosy & Other Mycobacterial Diseases (ICMR), Agra -282004, GuptaView Pramod B. KhedekarPramod KhedekarDepartment KhedekarView Rupesh V. Chikhale*Rupesh ChikhaleUCL School Pharmacy, Department Biological Chemistry, University College London, London WC1N 1AX, United Kingdom*Email: [email protected]More ChikhaleView Biographyhttps://orcid.org/0000-0001-5622-3981Cite this: Anal. Chem. 2024, XXXX, XXX, XXX-XXXPublication Date (Web):April 30, 2024Publication History Received18 November 2023Accepted15 April 2024Revised11 2024Published online30 2024https://doi.org/10.1021/acs.analchem.3c05225© 2024 The Authors. Published American Chemical Society. This publication is licensed under CC-BY 4.0. License Summary*You are free to share (copy redistribute) this article in any medium or format adapt (remix, transform, build upon) the material purpose, even commercially within parameters below:Creative Commons (CC): a Creative license.Attribution (BY): Credit must be given creator.View full license*DisclaimerThis summary highlights only some key features terms actual license. It not license has no legal value. Carefully review before using these materials. Open Access indicated. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views COUNTER-compliant sum text downloads since 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score quantitative measure attention that research received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (5 MB) Get e-AlertscloseSUBJECTS:Fluorescence,Genetics,Peptides proteins,Probes,SARS-CoV-2 e-Alerts

Language: Английский

Citations

6