Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.

Thongkoon Priengprom,Supawadee Suebsasana,Chamsai Pientong,Tipaya Ekalaksananan,Chantana Aromdee,Bunkerd Kongyingyoes

doi:10.1186/s12906-015-0591-x

Thongkoon Priengprom, Supawadee Suebsasana + Show 4 more

Open Access

https://doi.org/10.1186/s12906-015-0591-x

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Abstract

BackgroundAn andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). In this study, we examined the anti-viral activity of IPAD on HSV wild types (HSV-1 strain KOS and HSV-2 clinical isolate) and HSV-1 drug-resistant strains (DRs). Synergistic effects of IPAD with acyclovir (ACV) were also evaluated.MethodsMTT and cytopathic effect (CPE) reduction assays were performed to determine cytotoxicity and anti-viral activities, respectively. A combination assay was used to determine synergistic effects of IPAD and ACV. Presence of viral DNA and protein in experimental cells was investigated using the polymerase chain reaction and western blotting, respectively.ResultsA non-cytotoxic concentration of IPAD (20.50 μM) completely inhibited CPE formation induced by HSV wild types and HSV-1 DRs after viral entry into the cells. The anti-HSV activities included inhibition of viral DNA and protein synthesis. The minimum inhibitory concentrations of ACV for HSV wild types and HSV-1 DRs were 20.20 and 2,220.00 μM, respectively. Combination of ACV with IPAD showed synergistic effects in inhibition of CPE formation, viral DNA and protein synthesis by HSV wild types as well as HSV-1 DRs. For the synergistic effects on HSV wild types and HSV-1 DRs, the effective concentrations of ACV were reduced.ConclusionsThese results showed the inhibitory potential of IPAD on HSV wild types and HSV-1 DRs and suggested that IPAD could be used in combination with ACV for treatment of HSV-1 DRs infections.

Highlights

An andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1)
Cytotoxicity and anti-Herpes simplex viruses (HSV) activity of IPAD The maximum concentration of IPAD which did not affect Vero cell viability was 22.55 μM while the highest dose of ACV used in the experiment (6,400 μM) did not affect Vero cell viability
At the pre-entry step, 10 μM dextran sulfate exhibited 100% inhibition whereas 20.50-22.55 μM IPAD exerted about 50-60% inhibition against both HSV wild types and HSV-1 drug-resistant strains (DRs)

Summary

Introduction

3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). Long-term prophylactic and Priengprom et al BMC Complementary and Alternative Medicine (2015) 15:56 mutations conferring resistance to ACV have been mapped both in UL23 and UL30 genes, but 95% of HSV strains exhibiting resistance to ACV harbor mutations within the UL23 gene alone These mutations lead to the production of TK with deficient or altered phosphorylation activity. 3, 19-isopropylideneandrographolide (IPAD), an analogue of Androg, was found to exert an absolute inhibitory effect on HSV-1 post-infection at the concentration of 11.96 μM [7,8]. Its action influences viral DNA synthesis and expression of gC and gD [7]

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