Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity
Links to Files
Author/Creator ORCID
Date
Type of Work
Department
Program
Citation of Original Publication
Peters, Hannah L., Dirk Jochmans, Adriaan H. de Wilde, Clara C. Posthuma, Eric J. Snijder, Johan Neyts, and Katherine L. Seley-Radtke. “Design, Synthesis and Evaluation of a Series of Acyclic Fleximer Nucleoside Analogues with Anti-Coronavirus Activity.” Bioorganic & Medicinal Chemistry Letters 25, no. 15 (August 1, 2015): 2923–26. https://doi.org/10.1016/j.bmcl.2015.05.039.
Rights
This item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
Abstract
A series of doubly flexible nucleoside analogues were designed based on the acyclic sugar scaffold of acyclovir and the flex-base moiety found in the fleximers. The target compounds were evaluated for their antiviral potential and found to inhibit several coronaviruses. Significantly, compound 2 displayed selective antiviral activity (CC₅₀ >3× EC₅₀) towards human coronavirus (HCoV)-NL63 and Middle East respiratory syndrome-coronavirus, but not severe acute respiratory syndrome-coronavirus. In the case of HCoV-NL63 the activity was highly promising with an EC₅₀ <10 μM and a CC₅₀ >100 μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.