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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.
Müller, Christin; Obermann, Wiebke; Karl, Nadja; Wendel, Hans-Guido; Taroncher-Oldenburg, Gaspar; Pleschka, Stephan; Hartmann, Roland K; Grünweller, Arnold; Ziebuhr, John.
  • Müller C; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany; German Center for Infection Research (DZIF) at the Partner Site Giessen-Marburg-Langen, Germany.
  • Obermann W; Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, 35032, Marburg, Germany.
  • Karl N; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany.
  • Wendel HG; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10023, USA.
  • Taroncher-Oldenburg G; Gaspar Taroncher Consulting, Philadelphia, PA, 19119, USA.
  • Pleschka S; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany; German Center for Infection Research (DZIF) at the Partner Site Giessen-Marburg-Langen, Germany.
  • Hartmann RK; Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, 35032, Marburg, Germany.
  • Grünweller A; Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, 35032, Marburg, Germany. Electronic address: gruenwel@staff.uni-marburg.de.
  • Ziebuhr J; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392, Giessen, Germany; German Center for Infection Research (DZIF) at the Partner Site Giessen-Marburg-Langen, Germany.
Antiviral Res ; 186: 105012, 2021 02.
Article in English | MEDLINE | ID: covidwho-1064809
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1. Eukaryotic Initiation Factor-4A STIMULATES Protein Biosynthesis
Subject
Eukaryotic Initiation Factor-4A
Predicate
STIMULATES
Object
Protein Biosynthesis
2. Eukaryotic Initiation Factor-4A STIMULATES Protein Biosynthesis
Subject
Eukaryotic Initiation Factor-4A
Predicate
STIMULATES
Object
Protein Biosynthesis
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / Benzofurans / SARS-CoV-2 / Hydroxamic Acids Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105012

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Virus Replication / Benzofurans / SARS-CoV-2 / Hydroxamic Acids Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Antiviral Res Year: 2021 Document Type: Article Affiliation country: J.antiviral.2021.105012