Broad Antiviral Effects of Echinacea purpurea against SARS-CoV-2 Variants of Concern and Potential Mechanism of Action
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Abstract
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 EC50′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.
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SciScore for 10.1101/2021.12.12.472255: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources 2.3 SARS-CoV-2 pseudoparticle generation: Lentiviral pseudotyped viruses are generated in HEK293T cells which are transfected with a mixture of 0.6 µg p8.91 (HIV-1 gag-pol), 0.6 µg pCSFLW (lentivirus backbone expressing a firefly luciferase reporter gene), and 0.5 µg pcDNA3.1 SARS-CoV-2 Spike D614 in OptiMEM with 10 µl polyethyleneimine 1 µg/ml (Sigma) as previously described (Conceicao C, 2020). HEK293Tsuggested: NoneFor Vero E6 cells, toxicity assay has been carried out and reported earlier (Singer et al, 2020) 2.5 Virucidal Activity: Virucidal tests were carried out by the … SciScore for 10.1101/2021.12.12.472255: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources 2.3 SARS-CoV-2 pseudoparticle generation: Lentiviral pseudotyped viruses are generated in HEK293T cells which are transfected with a mixture of 0.6 µg p8.91 (HIV-1 gag-pol), 0.6 µg pCSFLW (lentivirus backbone expressing a firefly luciferase reporter gene), and 0.5 µg pcDNA3.1 SARS-CoV-2 Spike D614 in OptiMEM with 10 µl polyethyleneimine 1 µg/ml (Sigma) as previously described (Conceicao C, 2020). HEK293Tsuggested: NoneFor Vero E6 cells, toxicity assay has been carried out and reported earlier (Singer et al, 2020) 2.5 Virucidal Activity: Virucidal tests were carried out by the following facilities, that investigated the respective VOCs: B.1.1.7 (alpha), B1.351 (beta) and P.1 (gamma), Pleschka, University Giessen, Germany), B.1.1.7 (alpha), B1.617.2 (delta), AV.1 (Scotland) and B1.525 (eta) (Pariani, University Milano, Italy) OC43 (Vimalanathan, University British Columbia, Canada). Vero E6suggested: NoneFor infectious viral titer analysis, at 72 h post infection (hpi), cells were scraped from each well and collected with supernatant and viral titer was determined on HCT or Vero-E6 cells. Vero-E6suggested: NoneSoftware and Algorithms Sentences Resources Images were captured on Ziess Axio observer Z1 inverted fluorescent microscope (Zeiss, Germany) The fluorescent intensity was calculated using Imagej software (open source). Imagejsuggested: (ImageJ, RRID:SCR_003070)All the target proteins were processed by protein preparation wizard software (Schrodinger San Diago, Ca) and the ligands were constructed using LigPrep (Schrodinger San Diago, Ca). LigPrepsuggested: (Ligprep, RRID:SCR_016746)One-way ANOVA followed by Tukey multiple comparisons test was performed using GraphPad Prism version 9 (GraphPad Software, San Diego, USA). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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