Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Since 2019, SARS-CoV-2 has undergone mutations, resulting in pandemic and epidemic waves. The SARS-CoV-2 spike protein, crucial for cellular entry, binds to the ACE2 receptor exclusively when its receptor-binding domain (RBD) adopts the up-conformation. However, whether ACE2 also interacts with the RBD in the down-conformation to facilitate the conformational shift to RBD-up remains unclear. Herein, we present the structures of the BA.2.86 and the JN.1 spike proteins bound to ACE2. Notably, we successfully observed the ACE2-bound down-RBD, indicating an intermediate structure before the RBD-up conformation. The wider and mobile angle of RBDs in the up-state provides space for ACE2 to interact with the down-RBD, facilitating the transition to the RBD-up state. The K356T, but not N354-linked glycan, contributes to both of infectivity and neutralizing-antibody evasion in BA.2.86. These structural insights the spike-protein dynamics would help understand the mechanisms underlying SARS-CoV-2 infection and its neutralization.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458767 | PMC |
| http://dx.doi.org/10.1038/s41467-024-52808-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural Elucidation and Covalent Modulation of the Autorepressed Orphan Nuclear Receptor NR2F6.
ACS Chem Biol
September 2025
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute of Complex Molecular Systems, Technische Universiteit Eindhoven, 5612 AZ Eindhoven, The Netherlands.
The orphan nuclear receptor NR2F6 (Nuclear Receptor subfamily 2 group F member 6) is an emerging therapeutic target for cancer immunotherapy. Upregulation of NR2F6 expression in tumor cells has been linked to proliferation and metastasis, while in immune cells NR2F6 inhibits antitumor T-cell responses. Small molecule modulation of NR2F6 activity might therefore be a novel strategy in cancer treatment, benefiting from this dual role of NR2F6.
View Article and Find Full Text PDFSystemic Delivery of an mRNA-Encoding, Tumor-Activated Interleukin-12 Lock to Eliminate Tumors and Avoid Immune-Related Adverse Events.
Nano Lett
September 2025
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.
View Article and Find Full Text PDFResearch status of small molecule inhibitors, probes, and degraders of NSDs: a comprehensive review.
Future Med Chem
September 2025
Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou, P.R. China.
The nuclear receptor binding SET domain (NSD) family of histone methyltransferases, which comprised NSD1, NSD2, and NSD3. They play a pivotal role in catalyzing mono- and dimethylation of histone H3 at lysine 36 (H3K36me1/2), a modification critical for maintaining chromatin structure and transcriptional fidelity. Dysregulation of NSD enzymes, often through overexpression, mutation, or chromosomal translocation, has been implicated in a broad spectrum of malignancies and various diseases.
View Article and Find Full Text PDFA bivalent SARS-CoV-2 subunit vaccine for cats neutralizes both the original ancestral strain and BA.1 Pseudovirus carrying the 453F and 501 T mutation.
Vaccine
September 2025
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Hubei Jiangxia Laboratory, Wuhan 430200, China. Electronic address:
The spillover and spillback of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between humans and animals, especially companion animals, threaten global public health security. However, risk assessment of SARS-CoV-2 variants infecting companion animals and the development of corresponding prevention and control technologies are lacking. The aim of this study is to assess the potential risk of enhancement of the infectivity of SARS-CoV-2 in cats owing to mutations at key sites within the spike (S) protein receptor-binding domain (RBD) region and develop an efficient vaccine to cross-neutralize high-risk SARS-CoV-2 variants.
View Article and Find Full Text PDFIdentification of temperature-insensitive residues in regulating SARS-CoV-2 variants-human ACE2 interaction-a study of molecular dynamics simulation.
Phys Chem Chem Phys
September 2025
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, P. R. China.
The COVID-19 pandemic remains a global health crisis, with successive SARS-CoV-2 variants exhibiting enhanced transmissibility and immune evasion. Notably, the Omicron variant harbors extensive mutations in the spike protein's receptor-binding domain (RBD), altering viral fitness. While temperature is a critical environmental factor modulating viral stability and transmission, its molecular-level effects on variant-specific RBD-human angiotensin-converting enzyme 2 (hACE2) interactions remain underexplored.
View Article and Find Full Text PDF