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SARS-CoV-2 proteins

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

    Authors: Arnold Gruenweller; Christin Mueller; Wiebke Obermann; Nadja Karl; Hans G. Wendel; Gaspar Taroncher-Oldenburg; Stephan Pleschka; Roland K. Hartmann; John Ziebuhr; Ivet Bahar; Jinan Suliman; Elias Tayar; Hasan Ali Kasem; Meynard J. A. Agsalog; Bassam K. Akkarathodiyil; Ayat A. Alkhalaf; Mohamed Morhaf M. H. Alakshar; Abdulsalam Ali A. H. Al-Qahtani; Monther H. A. Al-Shedifat; Anas Ansari; Ahmad Ali Ataalla; Sandeep Chougule; Abhilash K. K. V. Gopinathan; Feroz J. Poolakundan; Sanjay U. Ranbhise; Saed M. A. Saefan; Mohamed M. Thaivalappil; Abubacker S. Thoyalil; Inayath M. Umar; Zaina Al Kanaani; Abdullatif Al Khal; Einas Al Kuwari; Adeel A. Butt; Peter Coyle; Andrew Jeremijenko; Anvar Hassan Kaleeckal; Ali Nizar Latif; Riyazuddin Mohammad Shaik; Hanan F. Abdul Rahim; Hadi M. Yassine; Gheyath K. Nasrallah; Mohamed G. Al Kuwari; Odette Chaghoury; Hiam Chemaitelly; Laith J Abu-Raddad

    doi:10.1101/2020.11.24.389627 Date: 2020-11-24 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), a betacoronavirus in the subgenus Sarbecovirus causes a respiratory disease MESHD with varying symptoms referred to as coronavirus disease 2019 MESHD ( COVID-19 MESHD) and is responsible for a pandemic that started in early 2020. With no vaccines or effective antiviral treatments available, and infection and fatality numbers continuing to increase globally, 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 positive- and negative-sense RNA viruses. This compound class inhibits eukaryotic initiation factor 4A ( eIF4A HGNC)-dependent mRNA translation initiation, resulting in strongly reduced viral RNA translation. The synthetic rocaglate CR-31-B (-) has previously been shown to inhibit the replication of human coronaviruses, such as HCoV-229E and MERS-CoV, as well as Zika-, Lassa-, Crimean Congo hemorrhagic fever MESHD virus in primary cells. Here, we assessed the antiviral activity of CR-31-B (-) against SARS-CoV-2 using both in vitro and ex vivo cell culture models. In African green monkey Vero E6 cells, CR-31-B (-) inhibited SARS-CoV-2 replication with an EC50 of ~1.8 nM. In line with this, viral protein accumulation and replication/transcription complex formation were found to be strongly reduced by this compound. In an ex vivo infection system using human airway epithelial cells, CR-31-B (-) was found to cause a massive reduction of SARS-CoV-2 MESHD titers by about 4 logs to nearly non-detectable levels. 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.

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MeSH Disease
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SARS-CoV-2 Proteins


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