Journal article

Publication year: 2021

Journal: Antiviral Research

Volume number: 186

ISSN: 0166-3542

eISSN: 1872-9096

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.antiviral.2021.105012

Publisher: Elsevier

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 similar to 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.

Harvard Citation style: Mueller, C., Obermann, W., Karl, N., Wendel, H., Taroncher-Oldenburg, G., Pleschka, S., et al. (2021) The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo, Antiviral Research, 186, Article 105012. https://doi.org/10.1016/j.antiviral.2021.105012

APA Citation style: Mueller, C., Obermann, W., Karl, N., Wendel, H., Taroncher-Oldenburg, G., Pleschka, S., Hartmann, R., Gruenweller, A., & Ziebuhr, J. (2021). The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo. Antiviral Research. 186, Article 105012. https://doi.org/10.1016/j.antiviral.2021.105012