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ID: ALA4340503

Journal: Bioorg Med Chem

Title: Antiviral activities of Janus-type nucleosides and their related oxime-intermediates.

Authors: Liu J, Zhao H, Zhou X, He Y, Chen Q.

Abstract: Herpes simplex virus (HSV) infection has been recognized as the most common mucosal disease in humans, manifesting as a life-threatening infection especially for patients with compromised immunity. When combined with the emergence of resistance due to the long-term use of classical antiviral agents, these threats make novel therapeutics for HSV a clinically necessity. We therefore designed and synthesized a series of Janus-type nucleosides by combining the natural genetic alphabets into a singular nucleoside structural unit. We also synthesized a series of new compounds and systematically evaluated their antiviral activity and structure-antiviral activity relationship. The results indicated that both nucleosides and their related intermediates exhibited high anti-HSV-1 activity. Compounds HY17 and HY19, in particular, possessed excellent anti-HSV-1 activity with IC50 values of 0.05 and 0.04 µg/mL, respectively. They also showed broad-spectrum antiviral activity against a multitude of diverse viruses, such as HSV-2, influenza virus A (H3N2), CVB3, HBV, HCV, and HPV. These results suggest that once their mechanisms are fully elucidated, these compounds will prove to be promising candidates as antiviral agents.

CiteXplore: 30578076

DOI: 10.1016/j.bmc.2018.12.014