The rocaglate CR-31-B (−) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo Journal Article


Authors: Müller, C.; Obermann, W.; Karl, N.; Wendel, H. G.; Taroncher-Oldenburg, G.; Pleschka, S.; Hartmann, R. K.; Grünweller, A.; Ziebuhr, J.
Article Title: The rocaglate CR-31-B (−) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, a severe respiratory disease with varying clinical presentations and outcomes, and responsible for a major pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, the quest for novel therapeutic solutions remains an urgent priority. Rocaglates, a class of plant-derived cyclopenta[b]benzofurans, exhibit broad-spectrum antiviral activity against multiple RNA viruses including coronaviruses. Specifically, rocaglates inhibit eukaryotic initiation factor 4A (eIF4A)-dependent mRNA translation initiation, resulting in strongly reduced viral RNA translation. Here, we assessed the antiviral activity of the synthetic rocaglate CR-31-B (−) against SARS-CoV-2 using both in vitro and ex vivo cell culture models. In Vero E6 cells, CR-31-B (−) inhibited SARS-CoV-2 replication with an EC50 of ~1.8 nM. In primary human airway epithelial cells, CR-31-B (−) reduced viral titers to undetectable levels at a concentration of 100 nM. Reduced virus reproduction was accompanied by substantially reduced viral protein accumulation and replication/transcription complex formation. The data reveal a potent anti-SARS-CoV-2 activity by CR-31-B (−), corroborating previous results obtained for other coronaviruses and supporting the idea that rocaglates may be used in first-line antiviral intervention strategies against novel and emerging RNA virus outbreaks. © 2021 The Authors
Keywords: translation initiation; antiviral activity; eif4a; covid-19; sars-cov-2; rocaglate
Journal Title: Antiviral Research
Volume: 186
ISSN: 0166-3542
Publisher: Elsevier Science, Inc.  
Date Published: 2021-02-01
Start Page: 105012
Language: English
DOI: 10.1016/j.antiviral.2021.105012
PROVIDER: scopus
PMCID: PMC7791309
PUBMED: 33422611
DOI/URL:
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
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  1. Hans Guido Wendel
    80 Wendel