Medicinal plants have long been recognized as a tremendous source of candidate compounds for the development of pharmaceuticals, including anti-viral agents. Herein, we report the identification of anti-influenza virus activity in non-polar Primula veris L. subsp. veris extracts. We show that P. veris subsp. veris flower extracts, obtained using supercritical fluid or ultrasound-based extraction, possess virucidal/virus inactivation properties and confer prophylactic and therapeutic effects against influenza virus-induced cytolysis in vitro. By GC-MS and UPLC-HRMS analysis of non-polar P. veris subsp. veris extracts we identified terpenes, flavones, tocopherols, and other classes of phytochemicals with known or putative anti-influenza properties. In silico prediction of cellular functions and molecular pathways affected by these phytochemicals suggests putative effects on signal transduction, inflammasome, and cell death pathways that are relevant to influenza virus pathogenesis. Combining P. veris subsp. veris with extracts of medicinal plants with proven anti-influenza activity such as Echinacea purpurea (L.) Moench and Cistus creticus L. subsp. creticus achieves an impressive protective effect against infection by influenza virus H1N1 in vitro and reduced progeny virus production by infected cells. Collectively, these findings uncover a previously uncharted biological property of non-polar P. veris flower extracts that warrants further studies to assess clinical efficacy.
Keywords: Cistus creticus; Echinaceae purpurea; Primula veris; influenza; supercritical extraction.