Results 121 to 130 of about 131,252 (300)

Switching Spike Plasticity Shapes ACE2 Engagement Across SARS‐CoV‐2 Variants

Advanced Science, EarlyView.
Conformational plasticity governs SARS‐CoV‐2 spike function and ACE2 recognition. Using high‐speed AFM and single‐molecule force spectroscopy, we analyzed the ancestral spike and nine variants, revealing progressive rigidification from Delta, variable plasticity in Omicron sublineages, and JN.1 compaction.
Sarah Stainer, Rong Zhu, Manuel Reithofer, Gerhard Stadlmayr, Katharina Stadlbauer, Panchika Prangkio, Christoph Rippel, Markus Hahn, Aniko Eva Kasztner, Stefanie Stohl, Petr Bednar, Daniel Ruzek, David Glück, Robert Tampé, Gordana Wozniak‐Knopp, Yoo Jin Oh, Miriam Klausberger, Peter Hinterdorfer   +17 more
wiley   +1 more source

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation

Advanced Science, EarlyView.
Dynamic supramolecular assembly reshapes targeted protein degradation by coordinating modular degrader construction, delivery, functional integration, and intracellular assembly or activation across proteasomal, endosomal–lysosomal, and autophagy–lysosomal pathways.
Kongjun Liu, Xue Yuan, Yan Zhou, Rui Yuan, Shaocheng Xie, Yong Chen, Peiyi Wang, Jianmei Gao, Qihai Gong   +8 more
wiley   +1 more source

Targeting β2‐Adrenergic Receptor Stability With Lycorine Reveals a Host‐Directed Pathway for Antiviral Defense Against Poxviruses

Advanced Science, EarlyView.
Chronic stress drives autophagy‐mediated β2‐AR degradation, impairing antiviral immunity and promoting poxvirus lethality. Lycorine directly stabilizes β2‐AR to restore host defense, suppress excessive inflammation and improve survival. ABSTRACT Psychological stress is a pervasive yet poorly understood modulator of infectious disease outcomes. Here, we
Xin Zhang, Shuqin Xu, Zixuan Zhang, Chenwen Wan, Xiaoqin Wang, Peihua Wang, Huini Yang, Tianxiao Huang, Yijia Yuan, Faiza Atique, Rui Yang, Yingli He, Zhijun Liu   +12 more
wiley   +1 more source

Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor

Nature Communications
Positive allosteric modulators (PAMs) of the μ opioid receptor (MOR) offer a promising path toward safer opioid therapeutics, yet their mechanisms of action remain poorly understood.
Haonan Zhang, Kirill Konovalov, Alexandra K. Parpounas, Davide Provasi, Shifan Yang, Alejandro Abraham, Aileen M. Vela, Audrey L. Warren, Gregory Zilberg, Suri Wang, Marta Filizola, Daniel Wacker   +11 more
doaj   +1 more source

Allosteric activators of cystathionine γ lyase to augment endogenous hydrogen sulfide and inhibit pathologic calcification

Pharmacological Research
Hydrogen sulfide (H₂S), a gasotransmitter naturally produced in the body by enzymes such as cystathionine γ lyase (CSE), helps reduce inflammation, oxidative stress, and abnormal tissue calcification.
Sonia Nasi, Driss Ehirchiou, Cindy Blatter, Veronique Chobaz, Stefan Germann, Alexandra Brandenberger, Elias Bommeli, Emiko Uchikawa, Giuseppe Cirino, Rainer Riedl, Alexander So, Nathalie Busso   +11 more
doaj   +1 more source

A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints

Advanced Science, EarlyView.
ARESEC is a synthetic platform that reconstructs functional V(D)J recombination in HEK293T cells. By introducing RSS elements and co‐expressing RAG1/2 and TdT across all three antibody CDRs, it enables programmable junctional diversification and direct generation of high‐affinity variants targeting PD‐1/PD‐L1, overcoming the evolutionary constraints of
Wang Liu, Jun Yang, Yuhang Zhang, Xiaoli Xue   +3 more
wiley   +1 more source

Targeting the PHB2–ACSL3 Lipid‐Remodeling Axis Overcomes Cisplatin Resistance by Restoring Ferroptosis in Gastric Cancer

Advanced Science, EarlyView.
ABSTRACT Platinum‐based chemotherapy resistance remains a major obstacle in gastric cancer (GC) treatment. Through integrated transcriptomic profiling of cisplatin‐resistant xenografts and pharmacogenomic interrogation of the NCI‐60 dataset, we identified Prohibitin‐2 (PHB2) as a previously unrecognized determinant of chemoresistance.
Liang Xu, Wanying Xiang, Xinyue Wang, Yue Pan, Jing Gao, Jiezhen Yang, Yufei Wang, Zhipu Zhu, Man Tong, Lei Jin, Yan Ye   +10 more
wiley   +1 more source

Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

Acta Pharmaceutica Sinica B
Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice. Unfortunately, current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful ...
Chunhao Zhu, Xiaobing Lan, Zhiqiang Wei, Jianqiang Yu, Jian Zhang   +4 more
doaj   +1 more source

Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A

Advanced Science, EarlyView.
Corynoxine exerts potent broad‐spectrum anticancer activity by directly targeting NQO1. This interaction dissociates the oncogenic NQO1‐PTPA complex, releasing PTPA to robustly activate the tumor suppressor PP2A. Consequently, downstream Raf/MEK/ERK and PI3K/AKT signaling pathways are suppressed, downregulating c‐Myc and driving tumor regression ...
Guoqing Hou, Li Lin, Mengjie Xia, Ruohan Liang, Yueyue Zhang, Linna Du, Xuan Cao   +6 more
wiley   +1 more source

Discovery of GluN2A subtype-selective N-methyl-d-aspartate (NMDA) receptor ligands

Acta Pharmaceutica Sinica B
The N-methyl-d-aspartate (NMDA) receptors, which belong to the ionotropic Glutamate receptors, constitute a family of ligand-gated ion channels. Within the various subtypes of NMDA receptors, the GluN1/2A subtype plays a significant role in central ...
Liyang Jiang, Na Liu, Fabao Zhao, Boshi Huang, Dongwei Kang, Peng Zhan, Xinyong Liu   +6 more
doaj   +1 more source