PROTAC-mediated degradation of HIV-1 Nef efficiently restores cell-surface CD4 and MHC-I expression and blocks HIV-1 replication

Emert-Sedlak, Lori A.; Tice, Colin M.; Shi, Haibin; Alvarado, John J.; Shu, Sherry T.; Reitz, Allen B.; Smithgall, Thomas E.

doi:10.1016/j.chembiol.2024.02.004

Cited by 5 publications

(1 citation statement)

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“…This approach aims to degrade pathogenic viral proteins by hijacking the ubiquitinproteasome system. While this technology is in its infancy, a very recent study reported promising results regarding PROTAC blocking HIV-1 replication through the selective degradation of HIV-1 Nef protein (3).…”

Section: Personalized Medicine: Tailoring Therapies To Individual Needsmentioning

confidence: 99%

COVID-19: the renaissance of science in the face of adversity

Perico,

Remuzzi

2024

Front. Sci.

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Unlike previous pandemics, COVID-19 emerged at a time when the world was intricately connected due to vast communication and technological advancements, igniting extensive collaboration and medical innovation.• Mathematical models and simulation tools proved invaluable for decision-makers to guide planning and responses across various governmental and private sectors, both nationally and globally. • Developments in omics-based technologies and systems biology are poised to drive advancements in our understanding of vaccinology, targeted treatments, and patient stratification-fostering a true era of personalized medicine. • By integrating computational analytics, artificial intelligence, telehealth, and digital therapeutics, we have unparalleled opportunities to take advantage of big data for informing personalized medicine strategies in the near future.

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Section: Personalized Medicine: Tailoring Therapies To Individual Needsmentioning

confidence: 99%

COVID-19: the renaissance of science in the face of adversity

Perico,

Remuzzi

2024

Front. Sci.

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PROTAC induces HIV-1 Nef degradation

Crunkhorn

2024

Nat Rev Drug Discov

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Targeted protein degradation: advances in drug discovery and clinical practice

Zhong,

Chang,

Xie

et al. 2024

Sig Transduct Target Ther

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Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function. This advanced technology capitalizes on the cell’s intrinsic proteolytic systems, including the proteasome and lysosomal pathways, to selectively eliminate disease-causing proteins. TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications. Despite its considerable potential, TPD faces challenges related to the properties of the drugs and their rational design. This review thoroughly explores the mechanisms and clinical advancements of TPD, from its initial conceptualization to practical implementation, with a particular focus on proteolysis-targeting chimeras and molecular glues. In addition, the review delves into emerging technologies and methodologies aimed at addressing these challenges and enhancing therapeutic efficacy. We also discuss the significant clinical trials and highlight the promising therapeutic outcomes associated with TPD drugs, illustrating their potential to transform the treatment landscape. Furthermore, the review considers the benefits of combining TPD with other therapies to enhance overall treatment effectiveness and overcome drug resistance. The future directions of TPD applications are also explored, presenting an optimistic perspective on further innovations. By offering a comprehensive overview of the current innovations and the challenges faced, this review assesses the transformative potential of TPD in revolutionizing drug development and disease management, setting the stage for a new era in medical therapy.

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PROTAC-mediated degradation of HIV-1 Nef efficiently restores cell-surface CD4 and MHC-I expression and blocks HIV-1 replication

Cited by 5 publications

References 50 publications

COVID-19: the renaissance of science in the face of adversity

COVID-19: the renaissance of science in the face of adversity

PROTAC induces HIV-1 Nef degradation

Targeted protein degradation: advances in drug discovery and clinical practice

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