Salvianolic acid A acts as a herpes simplex virus dual inhibitor by blocking glycoprotein B-mediated adsorption and membrane fusion.

BACKGROUND

The development of novel anti-herpes simplex virus (HSV) agents with high efficacy and low toxicity is great importance. Salvianolic acid A (SAA), a stilbenoid caffeic acid trimer from Salvia miltiorrhiza Bunge roots, has shown broad-spectrum antiviral activities against enterovirus 71 (EV71), pseudorabies virus (PRV), and SARS-CoV-2. However, no studies on its anti-HSV activity have been reported yet.

PURPOSE

To investigate the anti-HSV effects of SAA through both in vitro and in vivo approaches and to elucidate its mechanisms of action.

METHODS

The anti-HSV effects of SAA in vitro were determined by cytopathic effect (CPE) inhibition assay, western blot assay and viral plaque assay. The virucidal assay, drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA) and heparin binding assay investigated SAA's anti-HSV mechanism. The in vivo anti-HSV efficacy of SAA was evaluated using murine model for intranasal HSV-1 encephalitis and vaginal HSV-2 infection model.

RESULTS

SAA suppressed HSV-1 and HSV-2 multiplication in different cells with low toxicity, superior to acyclovir. SAA directly inactivates HSV by disrupting virion membrane. SAA interacts with viral surface glycoprotein B (gB) to block HSV adsorption and entry. SAA treatment significantly improved mice survival, attenuated inflammatory symptoms, and reduced viral titers in HSV-1 and HSV-2 infected mice.

CONCLUSION

SAA possesses significant anti-HSV effects in vitro and in vivo through interaction with gB to block HSV entry and cause HSV particle rupture and inactivation. These findings support its potential as a novel therapeutic agent for herpetic encephalitis and genital herpes.