Revolutionizing viral disease treatment: Phase separation and lysosome/exosome targeting as new areas and new paradigms for antiviral drug research

Du, Shaoqing; Hu, Xueping; Liu, Xinyong; Zhan, Peng

doi:10.1016/j.drudis.2024.103888

Cited by 4 publications

References 75 publications

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Viral Protein Dimerization Quality Control: A Design Strategy for a Potential Viral Inhibitor

Du,

Liu,

et al. 2024

J. Med. Chem.

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The global pharmaceutical market has been profoundly impacted by the coronavirus pandemic, leading to an increased demand for specific drugs. Consequently, drug resistance has prompted continuous innovation in drug design strategies to effectively combat resistant pathogens or disease variants. Protein dimers play crucial roles in vivo, including catalytic reactions, signal transduction, and structural stability. The site of action for protein dimerization modulators typically does not reside within the active site of the protein, thereby potentially impeding resistance development. Therefore, harnessing viral protein dimerization modulators could represent a promising avenue for combating viral infections. In this Perspective, we provide a detailed introduction to the design principles and applications of dimerization modulators in antiviral research. Furthermore, we analyze various representative examples to elucidate their modes of action while presenting our perspective on dimerization modulators along with the opportunities and challenges associated with this groundbreaking area of investigation. ■ SIGNIFICANCE • Significance: Targeting the modulation of the enzyme's dimerization has the potential to facilitate the development of novel therapeutic interventions that remain unaffected by cross-resistance to existing inhibitors. • Impact: The Perspective emphasizes the significance of protein dimerization in antiviral drug research and introduces novel design strategies for modulating protein dimerization. • Innovation: This Perspective explores the design and application of viral protein dimerization modulators, presenting novel avenues and challenges for further investigation.

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Viral Protein Dimerization Quality Control: A Design Strategy for a Potential Viral Inhibitor

Du,

Liu,

et al. 2024

J. Med. Chem.

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The latest developments in the design and discovery of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV

Li,

Ye,

Gao

et al. 2024

Expert Opinion on Drug Discovery

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Biophysical Mechanisms of Liquid–Liquid Phase Separation in Biological Systems

Uzorka,

Olaniyan,

Bawa

2024

Biophys. Rev. Lett.

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A key biophysical process in biological systems, liquid–liquid phase separation (LLPS) is responsible for constructing membrane-less organelles and modulating cellular activities. The biophysical mechanisms underlying LLPS are explored in this paper, with an emphasis on multivalent interactions, entropy-driven processes, and how they affect cellular organization. We investigate the impact of external stimuli on phase behavior and clarify the physiological roles of biomolecular condensates, from stress response modulation to gene expression regulation. In addition, we study dysregulated LLPS in human disorders, providing information about possible therapeutic targets and approaches to innovative therapeutics. Through this interdisciplinary approach, we aim to improve our knowledge of LLPS and its effects on health and illness, opening the door to new therapeutic approaches that focus on the behavior of proteins and the structure of cells.

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Revolutionizing viral disease treatment: Phase separation and lysosome/exosome targeting as new areas and new paradigms for antiviral drug research

Cited by 4 publications

References 75 publications

Viral Protein Dimerization Quality Control: A Design Strategy for a Potential Viral Inhibitor

Viral Protein Dimerization Quality Control: A Design Strategy for a Potential Viral Inhibitor

The latest developments in the design and discovery of non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the treatment of HIV

Biophysical Mechanisms of Liquid–Liquid Phase Separation in Biological Systems

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