Globalization and climate change have intensified the need to address the marginalization of R&D for neglected and zoonotic diseases. We propose that drug repurposing, using enabling technologies such as artificial intelligence, can address this need at a lower cost than de novo R&D processes.
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http://dx.doi.org/10.1016/j.tips.2024.10.012 | DOI Listing |
J Med Genet
December 2024
Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
Background: Clinical trials for rare disorders have unique challenges due to low prevalence, patient phenotype variability and high expectations. These challenges are highlighted by our study on clonazepam in patients, a common cause of intellectual disability. Previous studies on Arid1b-haploinsufficient mice showed positive effects of clonazepam on various cognitive aspects.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing 100094, China.
TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high-resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.
View Article and Find Full Text PDFACS Infect Dis
December 2024
Centre of Experimental Medicine and Surgery, Institute of Medical Sciences Banaras Hindu University, Varanasi-221005, U.P., India.
Protozoan parasite infections, particularly leishmaniasis, present significant public health challenges in tropical and subtropical regions, affecting socio-economic status and growth. Despite advancements in immunology, effective vaccines remain vague, leaving drug treatments as the primary intervention. However, existing medications face limitations, such as toxicity and the rise of drug-resistant parasites.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Beijing 100020, China.
Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.
View Article and Find Full Text PDFWound Repair Regen
December 2024
Department of Dermatology, University of California Davis School of Medicine, Sacramento, California, USA.
Bacterial biofilms represent a formidable challenge in the treatment of chronic wounds, largely because of their resistance to conventional antibiotics. The emergence of multidrug-resistant (MDR) bacterial strains exacerbates this issue, necessitating a shift towards exploring alternative therapeutic approaches. In response to this urgent need, there has been a surge in research efforts aimed at identifying effective non-antibiotic treatments.
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