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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Peters, Hannah L.¹  Jochmans, Dirk²  de Wilde, Adriaan H.³  Posthuma, Clara C.³  Snijder, Eric J.³  Neyts, Johan²  Seley-Radtke, Katherine L.¹ 

[1] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA

[2] Univ Leuven KULeuven, Rega Inst, BE-3000 Leuven, Belgium

[3] Leiden Univ, Med Ctr, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands

关键词: Fleximers;    Coronaviruses;    SARS;    MERS-CoV;    Nucleosides;    Acyclovir;    Antiviral;   

DOI  :  10.1016/j.bmcl.2015.05.039

来源: Elsevier

【 摘 要 】

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 >3x 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 mu M and a CC50 >100 mu M. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

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