2. Academic Validation
  3. Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity

Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity

  • Bioorg Med Chem Lett. 2015 Aug 1;25(15):2923-6. doi: 10.1016/j.bmcl.2015.05.039.
Hannah L Peters 1,  Dirk Jochmans 2,  Adriaan H de Wilde 3,  Clara C Posthuma 3,  Eric J Snijder 3,  Johan Neyts 2,  Katherine L Seley-Radtke 4
Affiliations

Affiliations

  • 1 University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
  • 2 Rega Institute, University of Leuven (KULeuven), Minderbroederstraat 10, Leuven BE-3000, Belgium.
  • 3 Leiden University Medical Center, Department of Medical Microbiology, PO Box 9600, 2300 RC Leiden, The Netherlands.
  • 4 University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: kseley@umbc.edu.
PMID: 26048809 DOI: 10.1016/j.bmcl.2015.05.039
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.

Keywords

Acyclovir; Antiviral; Coronaviruses; Fleximers; MERS-CoV; Nucleosides; SARS.

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