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

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 100μM. As such, these doubly flexible nucleoside analogues are viewed as a novel new class of drug candidates with potential for potent inhibition of coronaviruses.publisher: Elsevier articletitle: Design, synthesis and evaluation of a series of acyclic fleximer nucleoside analogues with anti-coronavirus activity journaltitle: Bioorganic & Medicinal Chemistry Letters articlelink: http://dx.doi.org/10.1016/j.bmcl.2015.05.039 content_type: article copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.status: publishe