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Background In our previous study, the semi-synthetic analog of andrographolide, 3,19-isopropylideneandrographolide (IPAD), acts more effectively against herpes simplex virus (HSV) infection in cell culture than does acyclovir. IPAD inhibits cytopathic effect and production of HSV wild types and drug-resistant strains. Its effect is associated with the reduction of immediate-early regulatory protein (ICP27) and early proteins (ICP8 and UL42), indicating a mode of action different from that of acyclovir. Therefore, studies of the anti-HSV activity of IPAD in animal models are required before further application.Material & Method Prednisolone-treated BALB/c mice were cutaneously infected with HSV-1 wild-type KOS strain. Experimental groups included control groups (untreated or treated only with the cream base) and treatment groups (with acyclovir or IPAD creams). Creams were applied four times daily for 10 days after infection to the relevant groups. The skin lesion score was assessed twice a day for 10 days. In addition, the effect of IPAD on HSV copy number and HSV late gene (gD) expression was investigated in skin lesion cells by quantitative real-time polymerase chain reaction.Result IPAD cream was significantly effective in delaying the development of skin lesions and regression of the skin lesion score by day 5 (P < 0.01) compared with untreated controls. In addition, this IPAD cream significantly reduced HSV DNA copy number and gD gene expression (P < 0.01). No signs of irritation were observed at the application site.Conclusion Topical administration of IPAD cream reduced skin lesions in mice cutaneously infected with HSV-1 KOS.

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.

Atypical bacterial pathogens—including Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Chlamydia trachomatis—are important infectious agents of the respiratory system. Most current information pertains to adults and little is known about the role of these organisms in lower respiratory tract infections among young children with acute bronchiolitis.

The E2 protein is expressed in the early stage of human papillomavirus (HPV) infection that is associated with cervical lesions. This protein plays important roles in regulation of viral replication and transcription. To characterize the role of E2 protein in modulation of cellular gene expression in HPV infected cells, genome-wide expression profiling of human primary keratinocytes (HPK) harboring HPV16 E2 and HPV18 E2 was investigated using microarray. The Principle Components Analysis (PCA) revealed that the expression data of HPV16 E2 and HPV18 E2-transduced HPKs were rather closely clustered. The Venn diagram of modulated genes showed an overlap of 10 common genes in HPV16 E2 expressing HPK and HPV18 E2 expressing HPK. These genes were expressed with significant difference by comparison with control cells. In addition, the distinct sets of modulated genes were detected 14 and 34 genes in HPV16 E2 and HPV18 E2 expressing HPKs, respectively.