A Potential Andrographolide Analogue against the Replication of Herpes Simplex Virus Type 1 in Vero Cells

Supawadee      Seubsasana; Chamsai      Pientong; Tipaya      Ekalaksananan; Sasithorn      Thongchai; Chantana      Aromdee

doi:10.2174/157340611795564268

Abstract

Andrographolide (AD), and 14-deoxyandrographolide (DAD) isolated from Andrographis paniculata Nees, Acanthaceae, and 3,19-isopropylideneandrographolide (IPAD), a semi-synthetic compound of AD, were examined for anti-HSV-1 activity in vitro. The inhibitory effects of these compounds on viral entry and replication steps were determined using pre- and post-infection assays, respectively. All the three compounds exhibited less than 50% inhibitory act against viral entry. In the post-infection, IPAD displayed absolute inhibition, whereas AD and DAD gave moderate activity. IPAD was selected to determine for the stage of anti-replication by time-of-addition and time-of-removal assays. From the time of removal assay, IPAD activity began after 4 h and completed at 16 h post infection which corresponded to the early genes expression. Its ability to inhibit HSV-1 was confirmed by polymerase chain reaction and the expression of viral glycoproteins C and D by western blot analysis. No viral enveloped glycoproteins D and C expressions were found. IPAD exhibited anti-HSV-1 replication relating to the early step of replication. Structure-activity relationships of andrographolide against HSV-1 was proposed, it is the first report of this ent-labdane diterpene.

Keywords: Andrographolide, antiviral replication, 14-deoxyandrographolide, 3,19-isopropylideneandrographolide, herpes simplex type 1, viral glycoprotein, DAD, Andrographis paniculata, post-infection assays, IPAD, anti-replication, HSV-1, western blot analysis, ent-labdane diterpene