Next Article in Journal
Key Roles of Dipterocarpaceae, Bark Type Diversity and Tree Size in Lowland Rainforests of Northeast Borneo—Using Functional Traits of Lichens to Distinguish Plots of Old Growth and Regenerating Logged Forests
Previous Article in Journal
High Prevalence of Carbapenemase-Producing Acinetobacter baumannii in Wound Infections, Ghana, 2017/2018
Previous Article in Special Issue
Antiviral Activity of Vacuolar ATPase Blocker Diphyllin against SARS-CoV-2
Review

Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics

1
Gaspar Taroncher Consulting, Philadelphia, PA 19119, USA
2
Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany
3
Partner Site Giessen-Marburg-Langen, German Center for Infection Research (DZIF), Hans-MeerweinStrasse 2, 35034 Marburg, Germany
4
Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, 35032 Marburg, Germany
*
Authors to whom correspondence should be addressed.
Academic Editor: Javier Sanchez-Cespedes
Microorganisms 2021, 9(3), 540; https://doi.org/10.3390/microorganisms9030540
Received: 29 January 2021 / Revised: 1 March 2021 / Accepted: 2 March 2021 / Published: 5 March 2021
(This article belongs to the Special Issue Antiviral Drug Discovery and Development in the Twenty-First Century)
The increase in pandemics caused by RNA viruses of zoonotic origin highlights the urgent need for broad-spectrum antivirals against novel and re-emerging RNA viruses. Broad-spectrum antivirals could be deployed as first-line interventions during an outbreak while virus-specific drugs and vaccines are developed and rolled out. Viruses depend on the host’s protein synthesis machinery for replication. Several natural compounds that target the cellular DEAD-box RNA helicase eIF4A, a key component of the eukaryotic translation initiation complex eIF4F, have emerged as potential broad-spectrum antivirals. Rocaglates, a group of flavaglines of plant origin that clamp mRNAs with highly structured 5′ untranslated regions (5′UTRs) onto the surface of eIF4A through specific stacking interactions, exhibit the largest selectivity and potential therapeutic indices among all known eIF4A inhibitors. Their unique mechanism of action limits the inhibitory effect of rocaglates to the translation of eIF4A-dependent viral mRNAs and a minor fraction of host mRNAs exhibiting stable RNA secondary structures and/or polypurine sequence stretches in their 5′UTRs, resulting in minimal potential toxic side effects. Maintaining a favorable safety profile while inducing efficient inhibition of a broad spectrum of RNA viruses makes rocaglates into primary candidates for further development as pan-antiviral therapeutics. View Full-Text
Keywords: pan-antiviral; rocaglates; eIF4A; silvestrol; CR-31-B; Zotatifin; translation initiation; coronavirus; COVID-19 pan-antiviral; rocaglates; eIF4A; silvestrol; CR-31-B; Zotatifin; translation initiation; coronavirus; COVID-19
Show Figures

Figure 1

MDPI and ACS Style

Taroncher-Oldenburg, G.; Müller, C.; Obermann, W.; Ziebuhr, J.; Hartmann, R.K.; Grünweller, A. Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics. Microorganisms 2021, 9, 540. https://doi.org/10.3390/microorganisms9030540

AMA Style

Taroncher-Oldenburg G, Müller C, Obermann W, Ziebuhr J, Hartmann RK, Grünweller A. Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics. Microorganisms. 2021; 9(3):540. https://doi.org/10.3390/microorganisms9030540

Chicago/Turabian Style

Taroncher-Oldenburg, Gaspar, Christin Müller, Wiebke Obermann, John Ziebuhr, Roland K. Hartmann, and Arnold Grünweller. 2021. "Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates—A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics" Microorganisms 9, no. 3: 540. https://doi.org/10.3390/microorganisms9030540

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop