Investigating the Anti-Herpes Simplex Virus-2 Potential of Phytochemicals Obtained from Polygonum aviculare

Abstract

Genital herpes is a sexually transmitted infection, caused by Herpes Simplex Virus-2. The virus is transmitted through body fluids and causes lesions and ulcers of the skin. The virus has the ability to cause secondary infections upon reactivation. To date, no vaccines have been reported against HSV-2. The most common antivirals used against HSV-2 include acyclovir, famciclovir and valacyclovir. These antivirals have reported adverse side effects in patients, including kidney injury and hepatotoxicity. Additionally, HSV-2 shows resistance against these antivirals. Polygonum aviculare, commonly known as knotweed or knotgrass, belongs to the family Polygonaceae. Various pharmacopoeias have reported its anti-oxidant, antibacterial, anti-fungal, anti-inflammatory and antiviral activities. However, its anitiviral activity against HSV-2 has not been reported yet. The main aim of this study is to highlight the anti-HSV-2 potential of phytochemicals from Polygonum aviculare using in-silico tools and techniques. Differential gene expression during genital herpes has been studied through analysis of microarray dataset and consensus sequence of HG52 and MS strains of HSV-2 has been built using high throughput sequencing dataset. This study also highlighted the binding pockets of non-structural HSV-2 proteins, which were not reported in the literature earlier. Microarray analysis results showed that 97 genes were constantly differentially expressed during different phases of genital herpes infection. Docking studies showed that Quercetin-3-O-rutinoside had the best binding affinity with various structural and non-structural proteins of HSV-2. Additionally, 15 new antiviral compounds were produced through fragment based drug design approach, which showed higher binding affinity with HSV-2 protein targets. Quantitative modelling of HSV-2 infection cycle showed that drug interaction with HSV-2 protein targets reduced virus titer. The in-silico analysis concluded that phytochemicals of Polygonum aviculare exhibit antiviral activity against HSV-2. These antiviral activities can be further verified through in vitro approaches.