Cryo-EM reveals binding of linoleic acid to SARS-CoV-2 spike glycoprotein, suggesting an antiviral treatment strategy DOI Creative Commons
Christine Toelzer, Kapil Gupta, Imre Berger

et al.

Acta Crystallographica Section D Structural Biology, Journal Year: 2023, Volume and Issue: 79(2), P. 111 - 121

Published: Jan. 20, 2023

The COVID-19 pandemic and concomitant lockdowns presented a global health challenge triggered unprecedented research efforts to elucidate the molecular mechanisms pathogenicity of SARS-CoV-2. spike glycoprotein decorating surface SARS-CoV-2 virions is prime target for vaccine development, antibody therapy serology as it binds host cell receptor central viral entry. electron cryo-microscopy structure protein revealed hydrophobic pocket in receptor-binding domain that occupied by an essential fatty acid, linoleic acid (LA). LA-bound adopts non-infectious locked conformation which more stable than infectious form shields important immunogenic epitopes. Here, impact LA binding on infectivity replication, evolutionary conservation other highly pathogenic coronaviruses, including variants concern (VOCs), are reviewed. importance metabolic products, eicosanoids, regulating human immune response inflammation highlighted. Lipid fatty-acid proteins virion appears be broader strategy employed viruses, picornaviruses Zika virus. Ligand stabilizes their assembly, downregulates infectivity. In case rhinoviruses, this has been exploited develop small-molecule antiviral drugs bind pocket. results suggest treatment based LA-binding

Language: Английский

The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature DOI Open Access
Angela Ishak, Meghana Mehendale, Mousa M. AlRawashdeh

et al.

Gene, Journal Year: 2022, Volume and Issue: 836, P. 146674 - 146674

Published: June 14, 2022

Language: Английский

Citations

41
Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain DOI Creative Commons

Héctor Hernández‐Parra,

Octavio D. Reyes‐Hernández, Gabriela Figueroa‐González

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: March 14, 2023

Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death are associated the entry of into Central Nervous System (CNS). This mini-review discusses main proposed mechanisms by which interacts blood-brain barrier (BBB) its involvement passage drugs CNS. We performed a search PubMed terms “COVID-19” “SARS-CoV-2” “blood-brain injury” “brain from year 2019 to 2022. found evidence that infects neurovascular cells increases BBB permeability increasing expression matrix metalloproteinase-9 degrades type IV collagen basement membrane through activating RhoA, induces restructuring cytoskeleton alters integrity barrier. The breakdown triggers severe inflammatory response, causing cytokine storm (release IL-1β, IL-6, TNF-α, etc.) characteristic phase COVID-19, includes recruitment macrophages lymphocytes activation astrocytes microglia. conclude increased would allow not reach brain normal physiological state, thus enhancing certain drugs’ beneficial adverse effects. hope this article will encourage research on impact COVID-19 recovered sequelae, focusing mainly possible dose adjustments changes pharmacokinetic parameters.

Language: Английский

Citations

30
Mutational dynamics of SARS-CoV-2: Impact on future COVID-19 vaccine strategies DOI Creative Commons
Niloofar Faraji,

Tahereh Zeinali,

Farahnaz Joukar

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e30208 - e30208

Published: April 25, 2024

The rapid emergence of multiple strains Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has sparked profound concerns regarding the ongoing evolution virus and its potential impact on global health. Classified by World Health Organization (WHO) as variants concern (VOC), these exhibit heightened transmissibility pathogenicity, posing significant challenges to existing vaccine strategies. Despite widespread vaccination efforts, continual SARS-CoV-2 presents a formidable obstacle achieving herd immunity. Of particular is coronavirus spike (S) protein, pivotal viral surface protein crucial for host cell entry infectivity. Mutations within S have been shown enhance confer resistance antibody-mediated neutralization, undermining efficacy traditional platforms. Moreover, undergoes molecular under selective immune pressure, leading diverse with distinct mutation profiles. This review underscores urgent need vigilance adaptation in development efforts combat evolving landscape mutations ensure long-term effectiveness immunization campaigns.

Language: Английский

Citations

13
Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology DOI Creative Commons
Alba Sebastián-Martín, Belén G. Sánchez, José María Mora-Rodríguez

et al.

Biomedicines, Journal Year: 2022, Volume and Issue: 10(8), P. 2026 - 2026

Published: Aug. 19, 2022

DPP4/CD26 is a single-pass transmembrane protein with multiple functions on glycemic control, cell migration and proliferation, the immune system, among others. It has recently acquired an especial relevance due to possibility act as receptor or co-receptor for SARS-CoV-2, it been already demonstrated other coronaviruses. In this review, we analyze evidence role of DPP4 COVID-19 risk clinical outcome, its contribution physiopathology. Due pathogenetic links between diabetes mellitus hyperinflammatory response, hallmark cytokine storm developed very often during disease, dive deep into carbohydrate metabolism system regulation. We show that broad spectrum regulated by performed both protease enzyme, well interacting partner molecules surface. addition, provide update inhibitors approved EMA and/or FDA, together newfangled approval generic drugs (in 2021 2022). This review will also cover effects (i.e., gliptins) progression SARS-CoV-2 infection, showing in disturbing disease.

Language: Английский

Citations

32
COVID-DSNet: A novel deep convolutional neural network for detection of coronavirus (SARS-CoV-2) cases from CT and Chest X-Ray images DOI Open Access
Hatice Çatal Reis, Veysel Turk

Artificial Intelligence in Medicine, Journal Year: 2022, Volume and Issue: 134, P. 102427 - 102427

Published: Oct. 17, 2022

Language: Английский

Citations

31
SARS-CoV-2 Spike Protein Is Capable of Inducing Cell–Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies DOI Creative Commons
Nina Reuter, Xiaohan Chen,

Barbara Kropff

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(7), P. 1500 - 1500

Published: July 4, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on complementation of GFP and luciferase to quantify fusogenic activity SARS-CoV-2 spike protein. provide several lines evidence that SARS-CoV-2, but not SARS-CoV-1, induced cell–cell fusion even in absence receptor, angiotensin-converting enzyme (ACE2). This poorly described ACE2-independent cell strictly dependent proteasomal cleavage furin while TMPRSS2 dispensable. Previous current variants concern (VOCs) differed significantly their fusogenicity. The Delta extremely potent compared Alpha, Beta, Gamma Kappa, Omicron almost devoid receptor-independent activity. Nonetheless, all analyzed variants, could be pharmacologically inhibited with CMK. Mapping studies revealed amino acids 652-1273 conferred Unexpectedly, residues proximal site were major relevance, whereas residue 655 critically regulated fusion. Finally, we found spike’s ACE2 antibodies directed against N-terminal domain (NTD) targeting receptor-binding (RBD). In conclusion, our BSL-1-compatible DSP allowed us screen inhibitors or interfere may therefore contribute both rational vaccine design development novel treatment options SARS-CoV-2.

Language: Английский

Citations

19
Quantitative profiling of N-glycosylation of SARS-CoV-2 spike protein variants DOI Creative Commons
Yongjing Xie, Michael Butler

Glycobiology, Journal Year: 2023, Volume and Issue: 33(3), P. 188 - 202

Published: Feb. 1, 2023

Abstract With the global spread of corona virus disease-2019 pandemic, new spike variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continuously emerge due to increased possibility adaptive amino acid mutations. However, N-glycosylation profiles different are yet be explored extensively, although protein is heavily glycosylated and surface glycans well-established play key roles in viral infection immune response. Here, we investigated quantitatively seven major emerging including Original, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Kappa (B.1.671.1), Delta (B.1.671.2), Omicron (B.1.1.529). The aim was understand changing pattern N-glycan SARS-CoV-2 evolution addition widely studied Different exhibit substantial variations relative abundance glycan peaks subclasses, no specific species exclusively present or absent from any variant. Cluster analysis shows that may hold potential for classification. closest similarity variant displays variants, while significantly its counterparts. We demonstrated there a quantifiable difference among variants. current study observations herein provide valuable framework quantitative profiling give us more comprehensive picture COVID-19 evolution.

Language: Английский

Citations

18
On the origins of SARS-CoV-2 main protease inhibitors DOI
Yves L. Janin

RSC Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 15(1), P. 81 - 118

Published: Oct. 13, 2023

In order to address the world-wide health challenge caused by COVID-19 pandemic, 3CL protease/SARS-CoV-2 main protease (SARS-CoV-2-M

Language: Английский

Citations

17
Advances in virus-like particle-based SARS-CoV-2 vaccines DOI Creative Commons
Xiaoting Hao,

Feifei Yuan,

Xuan Yao

et al.

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

Published: June 26, 2024

The Coronavirus Disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has incurred devastating human and economic losses. Vaccination remains most effective approach for controlling COVID-19 pandemic. Nonetheless, sustained evolution of SARS-CoV-2 variants provoked concerns among scientific community regarding development next-generation vaccines. Among these, given their safety, immunogenicity, flexibility to display varied native epitopes, virus-like particle (VLP)-based vaccines represent one promising In this review, we summarize advantages characteristics VLP platforms, strategies antigen display, current clinical trial progress based on platforms. Importantly, experience lessons learned from provide insights into prevent future pandemics other epidemics.

Language: Английский

Citations

6
Structural Study of SARS-CoV-2 Antibodies Identifies a Broad-Spectrum Antibody That Neutralizes the Omicron Variant by Disassembling the Spike Trimer DOI

Wuqiang Zhan,

Xiaolong Tian, Xiang Zhang

et al.

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(16)

Published: Aug. 4, 2022

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses new challenges in the fight against disease 2019 (COVID-19) pandemic. newly emerging Omicron strain caused serious immune escape and raised unprecedented concern all over world. development an antibody targeting a conserved universal epitope is urgently needed. A subset neutralizing antibodies (NAbs) COVID-19 from convalescent patients were isolated our previous study. In this study, we investigated accommodation these NAbs to SARS-CoV-2 (VOCs), revealing that IgG 553-49 neutralizes pseudovirus variant. addition, determined cryo-electron microscopy (cryo-EM) structure spike (S) protein complexed with three monoclonal different epitopes, including 553-49, 553-15, 553-60. Notably, targets virus by disassembling S trimers. VOCs except Omicron, cross-links two trimers form trimer dimer, demonstrating 553-15 steric hindrance virion aggregation. These findings suggest potential develop other highly as promising therapeutic reagents for COVID-19. IMPORTANCE higher escape, raising concerns about effectiveness therapies vaccines. identified antibody, which completely epitope. revealed cross-linking virions 553-60 functions blocking receptor binding. Comparison binding domain (RBD) epitopes hidden keeps high degree conservation during evolution, making reagent future SARS-CoV-2.

Language: Английский

Citations

26