دورية أكاديمية

Limited high-throughput screening compatibility of the phenuivirus cap-binding domain

التفاصيل البيبلوغرافية
العنوان: Limited high-throughput screening compatibility of the phenuivirus cap-binding domain
المؤلفون: Janna Scherf, Dominik Vogel, Sheraz Gul, Jeanette Reinshagen, Philip Gribbon, Maria Rosenthal
المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-9 (2023)
بيانات النشر: Nature Portfolio, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract Bunyaviruses constitute a large and diverse group of viruses encompassing many emerging pathogens, such as Rift Valley fever virus (family Phenuiviridae), with public and veterinary health relevance but with very limited medical countermeasures are available. For the development of antiviral strategies, the identification and validation of virus-specific targets would be of high value. The cap-snatching mechanism is an essential process in the life cycle of bunyaviruses to produce capped mRNAs, which are then recognized and translated into viral proteins by the host cell translation machinery. Cap-snatching involves cap-binding as well as endonuclease functions and both activities have been demonstrated to be druggable in related influenza viruses. Here, we explore the suitability of the phenuivirus cap-binding function as a target in medium- and high-throughput drug discovery approaches. We developed a range of in vitro assays aiming to detect the interaction between the cap-binding domain (CBD) and the analogue of its natural cap-ligand m7GTP. However, constricted by its shallow binding pocket and low affinity for m7GTP, we conclude that the CBD has limited small molecule targeting potential using classical in vitro drug discovery approaches.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-023-50158-5
URL الوصول: https://doaj.org/article/ed2572b2c26b4e398d7434b631e4b0ef
رقم الأكسشن: edsdoj.2572b2c26b4e398d7434b631e4b0ef
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-023-50158-5