Nejvíce citovaný článek - PubMed ID 37728236
Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors
The 37th International Conference on Antiviral Research (ICAR) was held in Gold Coast, Australia, May 20-24, 2024. ICAR 2024 featured over 75 presentations along with two poster sessions and special events, including those specifically tailored for trainees and early-career scientists. The meeting served as a platform for the exchange of cutting-edge research, with presentations and discussions covering novel antiviral compounds, vaccine development, clinical trials, and therapeutic advancements. A comprehensive array of topics in antiviral science was covered, from the latest breakthroughs in antiviral drug development to innovative strategies for combating emerging viral threats. The keynote presentations provided fascinating insight into two diverse areas fundamental to medical countermeasure development and use, including virus emergence at the human-animal interface and practical considerations for bringing antivirals to the clinic. Additional sessions addressed a variety of timely post-pandemic topics, such as the hunt for broad spectrum antivirals, combination therapy, pandemic preparedness, application of in silico tools and AI in drug discovery, the virosphere, and more. Here, we summarize all the presentations and special sessions of ICAR 2024 and introduce the 38th ICAR, which will be held in Las Vegas, USA, March 17-21, 2025.
- MeSH
- antivirové látky * terapeutické užití farmakologie MeSH
- COVID-19 MeSH
- farmakoterapie COVID-19 MeSH
- lidé MeSH
- objevování léků MeSH
- vyvíjení léků MeSH
- vývoj vakcíny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- kongresy MeSH
- Geografické názvy
- Austrálie MeSH
- Názvy látek
- antivirové látky * MeSH
The emergence of SARS-CoV-2, the causative agent of COVID-19, has highlighted the need for advanced antiviral strategies. Targeting the coronaviral methyltransferase nsp14, which is essential for RNA capping, offers a promising approach for the development of small-molecule inhibitors. We designed and synthesized a series of adenosine 5'-carboxamide derivatives as potential nsp14 inhibitors and identified coumarin analogs to be particularly effective. Structural modifications revealed the importance of the 5'-carboxyl moiety for the inhibitory activity, showing superior efficacy compared to other modifications. Notably, compound 18l (HK370) demonstrated high selectivity and favorable in vitro pharmacokinetic properties and exhibited moderate antiviral activity in cell-based assays. These findings provide a robust foundation for developing targeted nsp14 inhibitors as a potential treatment for COVID-19 and related diseases.
- Publikační typ
- časopisecké články MeSH