ABSTRACT
Introduction SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they may escape vaccination effectiveness. Broad-spectrum antivirals could complement and further enhance preventive benefits achieved through SARS-CoV-2 vaccination campaigns. Aim Testing the antiviral activity of Echinacea purpurea against VOCs and exploring underlying modes-of-action. Method A hydroethanolic extract of freshly harvested E. purpurea herb and roots (Echinaforce®, EF extract) was tested to inhibit infection of VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish) and B1.525 (eta). Molecular dynamics (MD) were used to study interaction of EF phytochemical markers with known pharmacological viral and host cell targets. Results EF broadly inhibited propagation of all tested SARS-CoV-2 VOCs at EC50 < 12.0 ;jg/ml. Treatment of epithelial cells with 20 jg/ml EF prevented sequential infection with SARS-CoV-2 (Hu-1). MD analyses showed for alkylamides, caftaric acid and feruoyl-tartaric constant binding affinity to spike proteins of all VOCs and to TMPRSS-2, a serine protease required for virus endocytosis. Conclusion EF extract exhibits virucidal activity against all tested SARS-CoV-2 VOCs and protects epithelial cells from infection.