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Targeting the DEAD-Box RNA Helicase eIF4A with Rocaglates-A Pan-Antiviral Strategy for Minimizing the Impact of Future RNA Virus Pandemics.
Taroncher-Oldenburg, Gaspar; Müller, Christin; Obermann, Wiebke; Ziebuhr, John; Hartmann, Roland K; Grünweller, Arnold.
  • Taroncher-Oldenburg G; Gaspar Taroncher Consulting, Philadelphia, PA 19119, USA.
  • Müller C; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany.
  • Obermann W; Partner Site Giessen-Marburg-Langen, German Center for Infection Research (DZIF), Hans-MeerweinStrasse 2, 35034 Marburg, Germany.
  • Ziebuhr J; Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, 35032 Marburg, Germany.
  • Hartmann RK; Institute of Medical Virology, Justus Liebig University Giessen, Schubertstrasse 81, 35392 Giessen, Germany.
  • Grünweller A; Partner Site Giessen-Marburg-Langen, German Center for Infection Research (DZIF), Hans-MeerweinStrasse 2, 35034 Marburg, Germany.
Microorganisms ; 9(3)2021 Mar 05.
Article in English | MEDLINE | ID: covidwho-1134191
Semantic information from SemMedBD (by NLM)
1. Eukaryotic Initiation Factor-4F|EIF4A2|EIF4E|EIF4G1 PART_OF translation initiation complex
Subject
Eukaryotic Initiation Factor-4F|EIF4A2|EIF4E|EIF4G1
Predicate
PART_OF
Object
translation initiation complex
2. EIF4A1 gene|EIF4A1 STIMULATES RN
Subject
EIF4A1 gene|EIF4A1
Predicate
STIMULATES
Object
RN
3. Eukaryotic Initiation Factor-4F|EIF4A2|EIF4E|EIF4G1 PART_OF translation initiation complex
Subject
Eukaryotic Initiation Factor-4F|EIF4A2|EIF4E|EIF4G1
Predicate
PART_OF
Object
translation initiation complex
4. EIF4A1 gene|EIF4A1 STIMULATES RNA, Messenger
Subject
EIF4A1 gene|EIF4A1
Predicate
STIMULATES
Object
RNA, Messenger
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines Language: English Year: 2021 Document Type: Article Affiliation country: Microorganisms9030540

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines Language: English Year: 2021 Document Type: Article Affiliation country: Microorganisms9030540