Anti-HSV-1 activity and Na+, K+-ATPase modulation from extracts and nanoemulsions of Myrciaria floribunda leaves

Na+, K+ATPase (NKA) has been proposed as an essential element for herpes simplex virus type 1 (HSV-1) infection, especially during the first 3 infection hours. This evidence is underscored by the antiviral activity of NKA classical inhibitors, commonly known as cardiac glycosides. In this study, we evaluated whether the anti-HSV-1 activity of extracts from Myrciaria floribunda leaves and nanomusified extracts would be related to blocking of ion pumping via NKA inhibition.

Cells VERO infected with strain HSV-1 or HSV-1 acyclovir (ACV)-resistant or not infected were treated or untreated with different concentrations of extracts to evaluate cell viability, HSV replication, viral particle inactivation, synergistic effect, changes regarding NKA activity in a pig kidney medulla preparation and Na+, K + ionic concentrations. We showed that all nanomusified extracts (crude, ethyl acetate, dichloromethane, butanolic, and hexanic) exhibited significant antiviral activity with low cytotoxicity. Furthermore, all extracellular nanomaterials reduced the viral titer, mainly by decreasing the attachment step, and enhanced antiviral activity when combined. Also exhibited antiviral activity against HSV-1 ACV-resistant (PAAR'5 strain). In addition, we demonstrated that crude and ethyl acetate extracts reduced NKA activity in a pig kidney medulla preparation. Alterations in Na+ or K+ concentrations in the presence of these extracts affected viral replication. Interestingly, an increase in K+ concentration favors viral replication, while increase in Na+ concentration impairs it.

We postulate that anti-HSV-1 activity of extracts (crude and ethyl acetate) from M. floribunda leaves and nanomusified may be correlated with K+ influx due to NKA inhibition.