Guy Boivin,Sheng-Xiang Lin,Melanie Martin,Arezki Azzi
申请号：
US13321377
公开号：
US08791299B2
申请日:
2010.05.19
申请国别(地区):
US
年份:
2014
代理人:
摘要：
3D protein modeling and virtual screening of commercially-available compounds were performed to identify new inhibitors of the herpesvirus DNA polymerase, a key enzyme in the viral replication cycle. Two compounds (Nos 2 and 9) were particularly active against HSV-1 and HSV-2 strains and one compound (No 3) inhibited specifically cytomegalovirus (CMV) strains (overall hit rate of 25%). Some of the tested compounds inhibited wild-type viruses and strains resistant to current antiviral agents. New chemical entity derivatives of compound 2 with binding potential to the DNA polymerase retained an excellent activity against HSV-1, HSV-2 and VZV like the parental compound, as well against strains resistant to current antiviral agents. These non-nucleosidic herpesvirus DNA polymerase inhibitors with in vitro activity against drug-resistant clinical isolates warrant further pre-clinical studies.
