Computational design of candidate multi-epitope vaccine against SARS-CoV-2 targeting structural (S and N) and non-structural (NSP3 and NSP12) proteins DOI
Zeeshan Ali, Jyothsna Volisha Cardoza, Srijita Basak

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(22), P. 13348 - 13367

Published: Feb. 6, 2023

The COVID-19 pandemic caused by SARS-CoV-2 virus has created a global damage and exposed the vulnerable side of scientific research towards novel diseases. intensity is huge, with mortality rates more than 6 million people worldwide in span 2 years. Considering gravity situation, scientists all across world are continuously attempting to create successful therapeutic solutions combat virus. Various vaccination strategies being devised ensure effective immunization against infection. spreads very rapidly, infection rate remarkably high other respiratory tract viruses. viral entry recognition host cell facilitated S protein N along NSP3 majorly responsible for genome assembly NSP12 performs polymerase activity RNA synthesis. In this study, we have designed multi-epitope, chimeric vaccine considering two structural (S protein) non-structural proteins (NSP3 NSP12) aim induce immune response generating antibodies these target replication cell. computational tools were used, reliability was verified using molecular docking, dynamics simulation studies silico. These demonstrate that shows steady interaction Toll like receptors good stability will be inducing strong specific body.Communicated Ramaswamy H. Sarma.

Language: Английский

Detergent modulates the conformational equilibrium of SARS-CoV-2 Spike during cryo-EM structural determination DOI Creative Commons
Shawn B. Egri, Xue Wang, Marco A. Díaz-Salinas

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 3, 2023

The Spike glycoprotein of SARS-CoV-2 mediates viral entry into the host cell via interaction between its receptor binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2). RBD has been reported to adopt two primary conformations, a closed conformation in which site is shielded unable interact with ACE2, an open that capable ACE2. Many structural studies have probed conformational space homotrimeric from SARS-CoV-2. However, how sample buffer conditions used during determination influence currently unclear. Here, we systematically explored impact commonly detergents on Spike. We show presence detergent, predominantly occupies state cryo-EM determination. absence such compaction was neither observed by cryo-EM, nor single-molecule FRET designed visualize movement solution real-time. Our results highlight highly sensitive nature composition determination, emphasize importance orthogonal biophysical approaches validate models obtained.

Language: Английский

Citations

12
ChAdOx1 COVID vaccines express RBD open prefusion SARS-CoV-2 spikes on the cell surface DOI Creative Commons
Tao Ni, Luiza Mendonça, Yanan Zhu

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107882 - 107882

Published: Sept. 12, 2023

Highlights•Subtomogram averaging of ChAdOx1 nCoV-19 spikes in situ at subnanometer resolution•HexaPro stabilizes the one-RBD-up prefusion spike conformation•In cryo-ET structure antigens provides rationale for vaccine optimizationSummaryVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proven to be an effective means decreasing COVID-19 mortality, hospitalization rates, and transmission. One vaccines deployed worldwide is nCoV-19, which uses adenovirus vector drive expression original SARS-CoV-2 on surface transduced cells. Using cryo-electron tomography subtomogram averaging, we determined native structures product expressed cell surfaces situ. We show that ChAdOx1-vectored expressing Beta variant produce abundant predominantly conformation. Furthermore, HexaPro-stabilized yields higher expression, enhanced RBD exposure, reduced shedding S1 compared wild type. demonstrate determination as a powerful studying antigen design options future development emerging novel variants broadly other infectious viruses.Graphical abstract

Language: Английский

Citations

12
Disposable graphene-oxide screen-printed electrode integrated with portable device for detection of SARS-CoV-2 in clinical samples DOI

P R Ramya,

Sayanti Halder,

K. Nagamani

et al.

Bioelectrochemistry, Journal Year: 2024, Volume and Issue: 158, P. 108722 - 108722

Published: April 28, 2024

Language: Английский

Citations

4
New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic DOI Creative Commons

Jonatan J. Carvajal,

Valeria García-Castillo,

Shelsy V. Cuellar

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 7, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the distress condition known as COVID-19. This disease broadly affects several physiological systems, including gastrointestinal, renal, and central nervous (CNS) significantly influencing patient’s overall quality of life. Additionally, numerous risk factors have been suggested, gender, body weight, age, metabolic status, renal health, preexisting cardiomyopathies, inflammatory conditions. Despite advances in understanding genome pathophysiological ramifications COVID-19, its precise origins remain elusive. SARS-CoV-2 interacts with a receptor-binding domain within angiotensin-converting enzyme (ACE2). receptor expressed various organs different species, humans, abundance. Although COVID-19 has multiorgan manifestations, main pathologies occur lung, pulmonary fibrosis, failure, embolism, secondary bacterial pneumonia. In post-COVID-19 period, sequelae may occur, which causes, direct action virus, alteration immune response, alterations during infection, among others. Recognizing serious adverse health effects associated it becomes imperative to comprehensively elucidate discuss existing evidence surrounding this viral those related subsequent consequences. review aims contribute comprehensive impact long-term on human health.

Language: Английский

Citations

4
Insights into SARS-CoV-2 structure: Approaches and action of SARS-CoV-2 main protease inhibitor DOI
Ilma Shakeel,

Aaliya Taiyab,

Aanchal Rathi

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 89 - 117

Published: Jan. 1, 2025

Language: Английский

Citations

0
Structural understanding of SARS-CoV-2 virus entry to host cells DOI Creative Commons

Kim Le,

Shrute Kannappan, Truc Kim

et al.

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: Nov. 2, 2023

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants virus have further exacerbated COVID-19 mortality and infection rates, emphasizing urgent need for effective preventive strategies. Understanding viral mechanism crucial developing therapeutics vaccines. The entry SARS-CoV-2 into host cells key step in pathway has been targeted drug development. Despite numerous reviews virus, there lack comprehensive focusing on structural aspects entry. In this review, we analyze changes Spike proteins during process, dividing process prebinding, receptor binding, proteolytic cleavage, membrane fusion steps. By understanding atomic-scale details entry, can better target intervention We also examine impacts mutations proteins, including Omicron variant, Structural information provides insights effects guide development Finally, discuss available structure-based approaches Overall, review detailed analysis highlighting its significance vaccines against COVID-19. Therefore, our emphasizes importance combating infection.

Language: Английский

Citations

10
Dual metal dual layer GAA NW–FET (DMDL–GAA–NW–FET) biosensor for label free SARS-CoV-2 detection DOI
Shivani Yadav, Sonam Rewari

Microsystem Technologies, Journal Year: 2023, Volume and Issue: 30(5), P. 565 - 582

Published: Nov. 17, 2023

Language: Английский

Citations

10
Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2 DOI Creative Commons

Larysa V. Yevsieieva,

Kateryna Lohachova, Alexander Kyrychenko

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(50), P. 35500 - 35524

Published: Jan. 1, 2023

The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in world healthcare system. Despite some progress creation of antiviral vaccines and mass vaccination population, number patients continues grow because spread new mutations. There is an urgent need for direct-acting drugs capable suppressing or stopping main mechanisms reproduction SARS-CoV-2. Several studies have shown that successful replication virus cell requires proteolytic cleavage protein structures virus. Two proteases are crucial replicating other coronaviruses: protease (Mpro) papain-like (PLpro). In this review, we summarize essential viral proteins required its life cycle as targets chemotherapy infection provide critical summary development against COVID-19 from drug repurposing strategy up molecular design novel covalent non-covalent agents inhibiting replication. We overview choice Mpro PLpro promising pharmacological impact on cycle.

Language: Английский

Citations

10
SARS-CoV-2 ORF3a drives dynamic dense body formation for optimal viral infectivity DOI Creative Commons
Stella Hartmann, Lisa Radochonski, Chengjin Ye

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 12, 2025

SARS-CoV-2 hijacks multiple organelles for virion assembly, of which the mechanisms have not been fully understood. Here, we identified a SARS-CoV-2-driven membrane structure named 3a dense body (3DB). 3DBs are unusual electron-dense and dynamic structures driven by accessory protein ORF3a via remodeling specific subset trans-Golgi network (TGN) early endosomal membrane. 3DB formation is conserved in related bat pangolin coronaviruses but was lost during evolution to SARS-CoV. During infection, recruits viral structural proteins spike (S) (M) undergoes fusion/fission maintain optimal unprocessed-to-processed ratio S on assembled virions. Disruption resulted virions with an abnormal processing rate, leading dramatic reduction entry efficiency. Our study uncovers crucial role maintaining maximal infectivity highlights its potential as target COVID-19 prophylactics therapeutics.

Language: Английский

Citations

0
Nanomaterial-Based Biosensors for SARS-CoV-2 and Future Epidemics DOI
Parsa Yari, Shuang Liang, Vinit Kumar Chugh

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(42), P. 15419 - 15449

Published: Oct. 12, 2023

ADVERTISEMENT RETURN TO ISSUEReviewNEXTNanomaterial-Based Biosensors for SARS-CoV-2 and Future EpidemicsParsa YariParsa YariDepartment of Electrical Computer Engineering, Texas Tech University, Lubbock, 79409, United StatesMore by Parsa YariView Biography, Shuang LiangShuang LiangDepartment Chemical Engineering Materials Science, University Minnesota, Minneapolis, Minnesota 55455, LiangView Biographyhttps://orcid.org/0000-0003-1491-2839, Vinit Kumar ChughVinit ChughDepartment ChughView Biographyhttps://orcid.org/0000-0001-7818-7811, Bahareh RezaeiBahareh RezaeiDepartment RezaeiView Shahriar MostufaShahriar MostufaDepartment MostufaView Biographyhttps://orcid.org/0000-0002-3326-4817, Venkatramana Divana KrishnaVenkatramana KrishnaDepartment Veterinary Population Medicine, St. Paul, 55108, KrishnaView Renata SahaRenata SahaDepartment SahaView Biographyhttps://orcid.org/0000-0002-0389-0083, Maxim C.-J. CheeranMaxim CheeranDepartment CheeranView Jian-Ping WangJian-Ping WangDepartment StatesDepartment WangView Biographyhttps://orcid.org/0000-0002-0687-3203, Jenifer Gómez-PastoraJenifer Gómez-PastoraDepartment Gómez-PastoraView Kai Wu*Kai WuDepartment States*Email: [email protected]More WuView Biographyhttps://orcid.org/0000-0002-9444-6112Cite this: Anal. Chem. 2023, 95, 42, 15419–15449Publication Date (Web):October 12, 2023Publication History Received7 April 2023Published online12 October inissue 24 2023https://pubs.acs.org/doi/10.1021/acs.analchem.3c01522https://doi.org/10.1021/acs.analchem.3c01522review-articleACS PublicationsCopyright © 2023 American SocietyRequest reuse permissionsArticle Views1214Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated to reflect usage leading up last few days.Citations number other articles citing this article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score is a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biopolymers,Gold,Metal nanoparticles,Peptides proteins,SARS-CoV-2 Get e-Alerts

Language: Английский

Citations

9