tetano
Editor, Senior Moderator
Antiviral Res
. 2021 Jan 7;105012.
doi: 10.1016/j.antiviral.2021.105012. Online ahead of print.
The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo
Christin M?ller[SUP] 1 [/SUP], Wiebke Obermann[SUP] 2 [/SUP], Nadja Karl[SUP] 3 [/SUP], Hans-Guido Wendel[SUP] 4 [/SUP], Gaspar Taroncher-Oldenburg[SUP] 5 [/SUP], Stephan Pleschka[SUP] 1 [/SUP], Roland K Hartmann[SUP] 2 [/SUP], Arnold Gr?nweller[SUP] 6 [/SUP], John Ziebuhr[SUP] 1 [/SUP]
Affiliations
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 cyclopentabenzofurans, 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 EC[SUB]50[/SUB] 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.
Keywords: COVID-19; SARS-CoV-2; antiviral activity; eIF4A; rocaglate; translation initiation.
. 2021 Jan 7;105012.
doi: 10.1016/j.antiviral.2021.105012. Online ahead of print.
The rocaglate CR-31-B (-) inhibits SARS-CoV-2 replication at non-cytotoxic, low nanomolar concentrations in vitro and ex vivo
Christin M?ller[SUP] 1 [/SUP], Wiebke Obermann[SUP] 2 [/SUP], Nadja Karl[SUP] 3 [/SUP], Hans-Guido Wendel[SUP] 4 [/SUP], Gaspar Taroncher-Oldenburg[SUP] 5 [/SUP], Stephan Pleschka[SUP] 1 [/SUP], Roland K Hartmann[SUP] 2 [/SUP], Arnold Gr?nweller[SUP] 6 [/SUP], John Ziebuhr[SUP] 1 [/SUP]
Affiliations
- PMID: 33422611
- DOI: 10.1016/j.antiviral.2021.105012
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 cyclopentabenzofurans, 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 EC[SUB]50[/SUB] 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.
Keywords: COVID-19; SARS-CoV-2; antiviral activity; eIF4A; rocaglate; translation initiation.