2. Academic Validation
  3. Antiviral activities of Janus-type nucleosides and their related oxime-intermediates

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

  • Bioorg Med Chem. 2019 Jun 15;27(12):2332-2339. doi: 10.1016/j.bmc.2018.12.014.
Jiang Liu 1,  Hang Zhao 1,  Xinglong Zhou 2,  Yang He 3,  Qianming Chen 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Medicine of West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China.
  • 2 School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610041, PR China.
  • 3 Department of Respiratory and Critical Care Medicine Targeted Tracer Research and Development Laboratory West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: [email protected].
  • 4 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Medicine of West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address: [email protected].
PMID: 30578076 DOI: 10.1016/j.bmc.2018.12.014
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.

Keywords

Anti-HSV-1; Janus-type nucleosides; Oxime; Structure-antiviral activity relationship.

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