| Autor: |
Vimalanathan S; Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada., Shehata M; Institute of Medical Virology, Justus Liebig University Giessen, 35392 Giessen, Germany.; Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt., Sadasivam K; Centre for High Computing, Central Leather Research Institute, Adyar, Chennai 600020, India., Delbue S; Laboratory of Molecular Virology, Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy., Dolci M; Laboratory of Molecular Virology, Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy., Pariani E; Department of Biomedical Sciences for Health, University of Milano, 20133 Milano, Italy., D'Alessandro S; Department of Pharmacological and Biomedical Sciences, University of Milano, 20133 Milano, Italy., Pleschka S; Institute of Medical Virology, Justus Liebig University Giessen, 35392 Giessen, Germany.; German Center for Infection Research, Partner Site Giessen-Marburg-Langen, 35392 Giessen, Germany. |
| Abstrakt: |
SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity of Echinacea purpurea (Echinaforce ® extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish), B1.525 (eta), and B.1.1.529.BA1 (omicron); (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and reference strain OC43 as well as (iii) wild type SARS-CoV-2 (Hu-1) was analyzed. Molecular dynamics (MD) were applied to study the interaction of Echinacea's phytochemical markers with known pharmacological viral and host cell targets. EF extract broadly inhibited the propagation of all investigated SARS-CoV-2 VOCs as well as the entry of SARS-CoV-2 pseudoparticles at EC 50' s ranging from 3.62 to 12.03 µg/mL. The preventive addition of 25 µg/mL EF to epithelial cells significantly reduced sequential infection with SARS-CoV-2 (Hu-1) and OC43. MD analyses showed constant binding affinities to VOC-typical S protein variants for alkylamides, caftaric acid, and feruloyl-tartaric acid in EF extract and interactions with serine protease TMPRSS-2. EF extract demonstrated stable virucidal activity across seven tested VOCs, likely due to the constant affinity of the contained phytochemical substances to all spike variants. A possible interaction of EF with TMPRSS-2 partially would explain the cell protective benefits of the extract by the inhibition of membrane fusion and cell entry. EF may therefore offer a supportive addition to vaccination endeavors in the control of existing and future SARS-CoV-2 virus mutations. |
