Chemical Biology and Drug Design
Chemical Biology and Drug Design
5 years ago

Sofosbuvir as treatment against dengue?

Sofosbuvir as treatment against dengue?
Choon Han Heh, Rohana Yusof, Chin Fei Chee, See Khai Lim, Chye Sheng Gan
Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur was made available since 2015. However, administration of CTD-TDV in general has not received the prequalification recommendation from the World Health Organization. Having a universal anti-dengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study it's in silico and in vitro effects against dengue. As a result, the active metabolite of sofosbuvir (GS-461203) was predicted to bind to the catalytic motif (Gly-Asp-Asp) of dengue viral polymerase with binding affinity of -6.9 kcal/mol. Furthermore, sofosbuvir demonstrated excellent in vitro viral inhibition with an EC90 of 0.4 μM. In addition, this study demonstrated the requirement of specific liver enzymes to activate the prodrug into GS-461203 to exert its anti-dengue potential. All and all, sofosbuvir should be subjected to in depth studies to provide information of its efficacy towards dengue and its lead potential as DENV polymerase inhibitor in human subjects. In conclusion, we have expended the potential of the clinically available drug sofosbuvir as treatment for dengue. This article is protected by copyright. All rights reserved. Molecular docking of the activated structure of sofosbuvir, GS-461203, was performed on dengue virus polymerase. The findings were then validated using in vitro model of dengue virus infection. This study revealed the potential antidengue activity of sofosbuvir, and GS-461203 could serve as a lead compound in the development of novel antiviral agents against dengue virus.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13091

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.