Cousins David L, Griffen Ed J, Stacey Jessica, Lee Alpha A, Filimonova Yuliia, Hlavin Anton, Holota Yuliia, Khmil Roman, Kordubailo Mykyta, Kostinov Oleksii, Lesyk Dmytro, Logvinenko Ivan, Lototska Mariia, Lysenko Viacheslav, Pashchenko Anna, Pavlichenko Mariia, Rodnichenko Anzhela, Tkachenko Anton, Hurst Brett L, Julander Justin G, Wang Hong, Pearl Rebecca, Benjamin Jared, Diaz-Tapia Randy, Gordon Mary E, Albrecht Randy A, White Kris
MedChemica Consultancy Ltd, Macclesfield, Cheshire, SK11 6DU, UK.
The ASAP Discovery Consortium.
bioRxiv. 2025 Aug 12:2025.08.08.668114. doi: 10.1101/2025.08.08.668114.
Non-polio enteroviruses (NPEV) such as enterovirus D68 (EV-D68) that are highly infectious and associated with polio-like neurological complications have caused outbreaks, globally, in recent years. While some clinical and preclinical compounds have shown efficacy against NPEV , liabilities that caused historical compounds such as pleconaril to fall short of FDA approval still remain. We present herein SAR and SPR studies of analogues of clinical compounds such as pleconaril and vapendavir against EV-D68 as a representative NPEV. Numerous structurally differentiated analogues with EV-D68 antiviral activity and useful ADME properties were discovered, which could serve as starting points for future EV drug discovery campaigns. Screening against a panel of enteroviruses revealed moderately broad-spectrum anti-EV activity of compound 26.
近年来，诸如肠道病毒D68（EV-D68）等非脊髓灰质炎肠道病毒（NPEV）具有高度传染性，并与类脊髓灰质炎神经并发症相关，已在全球范围内引发疫情。虽然一些临床和临床前化合物已显示出对NPEV的疗效，但导致如普来可那立等历史化合物未获美国食品药品监督管理局（FDA）批准的缺陷仍然存在。我们在此展示了针对作为代表性NPEV的EV-D68，对诸如普来可那立和法匹拉韦等临床化合物类似物的构效关系（SAR）和表面等离子体共振（SPR）研究。发现了许多具有EV-D68抗病毒活性和有用的药物代谢及药代动力学（ADME）特性的结构不同的类似物，它们可作为未来EV药物研发活动的起点。针对一组肠道病毒的筛选显示化合物26具有适度的广谱抗EV活性。
