Anti-Herpes Simplex Virus (Wild-Type and Drug-Resistant) Properties of Herbal KerraTM, KSTM, and MinozaTM

Commercial herbal compounds are a main attractive target to explore for a novel drug for the treatment of HSV. This study investigated the anti-HSV infectivity of extracts derived from the Thai commercial herbals Kerra^TM, KS^TM, and Minoza^TM. Wild-type HSV-1 KOS, HSV-2, and drug-resistant HSV-1 dxpIII were used to investigate any inhibitory effects of these extracts. A plaque formation assay was performed to investigate the effects of all extracts. The viral <i>ICP4</i>, <i>UL30</i>, <i>gD</i>, and gB and cellular <i>IL1β</i>, <i>IL6</i>, <i>STAT3</i>, and <i>NFKB1</i> expression levels were evaluated. The Kerra^TM, KS^TM, and Minoza^TM extracts at 50-200 μg/mL significantly inhibited HSV-1 KOS and dxpIII infection in the post-entry step, whereas only Minoza^TM could not reduce plaque formation of HSV-2. In addition, <i>ICP4</i>, <i>UL30</i>, and <i>gD</i> mRNAs and gB protein were significantly decreased in Kerra^TM- and KS^TM-treated cells. Furthermore, <i>IL1B</i>, <i>IL6</i>, <i>STAT3</i>, and <i>NFKB1</i> expression was upregulated in Kerra^TM- and KS^TM-treated cells. Kerra^TM and KS^TM could be agents against HSV infection, especially the HSV acyclovir (ACV)-resistant strain. From the docking result and drug-likeness prediction, 2-Methoxy-9H-xanthen-9-one, piperine, and sargassopenilline D found in Kerra^TM, KS^TM, and Minoza^TM show high binding energy closely resembling ACV, and are desirable as drug-like characteristics.