MersV1, Main, Exploration, bibRecord, 000E74

Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

Identifieur interne : 000E74 ( Main/Exploration ); précédent : 000E73; suivant : 000E75

Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

Auteurs : Christin Müller [Allemagne] ; Falk W. Schulte [Allemagne] ; Kerstin Lange-Grünweller [Allemagne] ; Wiebke Obermann [Allemagne] ; Ramakanth Madhugiri [Allemagne] ; Stephan Pleschka [Allemagne] ; John Ziebuhr [Allemagne] ; Roland K. Hartmann [Allemagne] ; Arnold Grünweller [Allemagne]

Source :

Antiviral Research [ 0166-3542 ] ; 2017.

RBID : PMC:7113723

Descripteurs français

KwdFr :
- Animaux, Antiviraux (pharmacologie), Cellules Vero, Expression des gènes, Facteurs de transcription (antagonistes et inhibiteurs), Gènes rapporteurs, Humains, Lignée cellulaire, Picornaviridae (), Protéines de liaison à l'ADN (antagonistes et inhibiteurs), Relation dose-effet des médicaments, Régulation de l'expression des gènes viraux (), Triterpènes (pharmacologie).
MESH :
- antagonistes et inhibiteurs : Facteurs de transcription, Protéines de liaison à l'ADN.
- pharmacologie : Antiviraux, Triterpènes.
- Animaux, Cellules Vero, Expression des gènes, Gènes rapporteurs, Humains, Lignée cellulaire, Picornaviridae, Relation dose-effet des médicaments, Régulation de l'expression des gènes viraux.

English descriptors

KwdEn :
- Animals, Antiviral Agents (pharmacology), Cell Line, Chlorocebus aethiops, DNA-Binding Proteins (antagonists & inhibitors), Dose-Response Relationship, Drug, Gene Expression, Gene Expression Regulation, Viral (drug effects), Genes, Reporter, Humans, Picornaviridae (drug effects), Transcription Factors (antagonists & inhibitors), Triterpenes (pharmacology), Vero Cells.
MESH :
- chemical , antagonists & inhibitors : DNA-Binding Proteins, Transcription Factors.
- chemical , pharmacology : Antiviral Agents, Triterpenes.
- drug effects : Gene Expression Regulation, Viral, Picornaviridae.
- Animals, Cell Line, Chlorocebus aethiops, Dose-Response Relationship, Drug, Gene Expression, Genes, Reporter, Humans, Vero Cells.

Abstract

Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5′ cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent inhibitor of cap-dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells. EC₅₀ values of 1.3 nM and 3 nM silvestrol were determined for MERS-CoV and HCoV-229E, respectively. For the highly pathogenic MERS-CoV, the potent antiviral activities of silvestrol were also confirmed using peripheral blood mononuclear cells (PBMCs) as a second type of human primary cells. Silvestrol strongly inhibits the expression of CoV structural and nonstructural proteins (N, nsp8) and the formation of viral replication/transcription complexes. Furthermore, potential antiviral effects against human rhinovirus (HRV) A1 and poliovirus type 1 (PV), representing different species in the genus Enterovirus (family Picornaviridae), were investigated. The two viruses employ an internal ribosomal entry site (IRES)-mediated translation initiation mechanism. For PV, which is known to require the activity of eIF4A, an EC₅₀ value of 20 nM silvestrol was determined in MRC-5 cells. The higher EC₅₀ value of 100 nM measured for HRV A1 indicates a less critical role of eIF4A activity in HRV A1 IRES-mediated translation initiation. Taken together, the data reveal a broad-spectrum antiviral activity of silvestrol in infected primary cells by inhibiting eIF4A-dependent viral mRNA translation.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113723

DOI: 10.1016/j.antiviral.2017.12.010
PubMed: 29258862
PubMed Central: 7113723

Affiliations:

Le document en format XML

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<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>DNA-Binding Proteins (antagonists & inhibitors)</term>
<term>Dose-Response Relationship, Drug</term>
<term>Gene Expression</term>
<term>Gene Expression Regulation, Viral (drug effects)</term>
<term>Genes, Reporter</term>
<term>Humans</term>
<term>Picornaviridae (drug effects)</term>
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<term>Triterpenes (pharmacology)</term>
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</keywords>
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<term>Antiviraux (pharmacologie)</term>
<term>Cellules Vero</term>
<term>Expression des gènes</term>
<term>Facteurs de transcription (antagonistes et inhibiteurs)</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Picornaviridae ()</term>
<term>Protéines de liaison à l'ADN (antagonistes et inhibiteurs)</term>
<term>Relation dose-effet des médicaments</term>
<term>Régulation de l'expression des gènes viraux ()</term>
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</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Protéines de liaison à l'ADN</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Gene Expression Regulation, Viral</term>
<term>Picornaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
<term>Triterpènes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cell Line</term>
<term>Chlorocebus aethiops</term>
<term>Dose-Response Relationship, Drug</term>
<term>Gene Expression</term>
<term>Genes, Reporter</term>
<term>Humans</term>
<term>Vero Cells</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cellules Vero</term>
<term>Expression des gènes</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Picornaviridae</term>
<term>Relation dose-effet des médicaments</term>
<term>Régulation de l'expression des gènes viraux</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5′ cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent inhibitor of cap-dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells. EC<sub>50</sub>
 values of 1.3 nM and 3 nM silvestrol were determined for MERS-CoV and HCoV-229E, respectively. For the highly pathogenic MERS-CoV, the potent antiviral activities of silvestrol were also confirmed using peripheral blood mononuclear cells (PBMCs) as a second type of human primary cells. Silvestrol strongly inhibits the expression of CoV structural and nonstructural proteins (N, nsp8) and the formation of viral replication/transcription complexes. Furthermore, potential antiviral effects against human rhinovirus (HRV) A1 and poliovirus type 1 (PV), representing different species in the genus <italic>Enterovirus</italic>
 (family <italic>Picornaviridae</italic>
), were investigated. The two viruses employ an internal ribosomal entry site (IRES)-mediated translation initiation mechanism. For PV, which is known to require the activity of eIF4A, an EC<sub>50</sub>
 value of 20 nM silvestrol was determined in MRC-5 cells. The higher EC<sub>50</sub>
 value of 100 nM measured for HRV A1 indicates a less critical role of eIF4A activity in HRV A1 IRES-mediated translation initiation. Taken together, the data reveal a broad-spectrum antiviral activity of silvestrol in infected primary cells by inhibiting eIF4A-dependent viral mRNA translation.</p>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Biedenkopf, N" uniqKey="Biedenkopf N">N. Biedenkopf</name>
</author>
<author><name sortKey="Lange Grunweller, K" uniqKey="Lange Grunweller K">K. Lange-Grünweller</name>
</author>
<author><name sortKey="Schulte, F W" uniqKey="Schulte F">F.W. Schulte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bordeleau, M E" uniqKey="Bordeleau M">M.E. Bordeleau</name>
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<author><name sortKey="Mori, A" uniqKey="Mori A">A. Mori</name>
</author>
<author><name sortKey="Oberer, M" uniqKey="Oberer M">M. Oberer</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cencic, R" uniqKey="Cencic R">R. Cencic</name>
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<author><name sortKey="Carrier, M" uniqKey="Carrier M">M. Carrier</name>
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<author><name sortKey="Galicia Vazquez, G" uniqKey="Galicia Vazquez G">G. Galicia-Vázquez</name>
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</analytic>
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<biblStruct><analytic><author><name sortKey="Chu, J" uniqKey="Chu J">J. Chu</name>
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<author><name sortKey="Galicia Vazquez, G" uniqKey="Galicia Vazquez G">G. Galicia-Vázquez</name>
</author>
<author><name sortKey="Cencic, R" uniqKey="Cencic R">R. Cencic</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hinnebusch, A G" uniqKey="Hinnebusch A">A.G. Hinnebusch</name>
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<author><name sortKey="Ivanov, I P" uniqKey="Ivanov I">I.P. Ivanov</name>
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<author><name sortKey="Sonenberg, N" uniqKey="Sonenberg N">N. Sonenberg</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kogure, T" uniqKey="Kogure T">T. Kogure</name>
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<author><name sortKey="Kinghorn, A D" uniqKey="Kinghorn A">A.D. Kinghorn</name>
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<author><name sortKey="Yan, I" uniqKey="Yan I">I. Yan</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, K M" uniqKey="Lee K">K.M. Lee</name>
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<author><name sortKey="Chen, C J" uniqKey="Chen C">C.J. Chen</name>
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<author><name sortKey="Shih, S R" uniqKey="Shih S">S.R. Shih</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lucas, D M" uniqKey="Lucas D">D.M. Lucas</name>
</author>
<author><name sortKey="Edwards, R B" uniqKey="Edwards R">R.B. Edwards</name>
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<author><name sortKey="Lozanski, G" uniqKey="Lozanski G">G. Lozanski</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lundin, A" uniqKey="Lundin A">A. Lundin</name>
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<author><name sortKey="Dijkman, R" uniqKey="Dijkman R">R. Dijkman</name>
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<author><name sortKey="Kann, N" uniqKey="Kann N">N. Kann</name>
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<author><name sortKey="Adamiak, B" uniqKey="Adamiak B">B. Adamiak</name>
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<author><name sortKey="Hannoun, C" uniqKey="Hannoun C">C. Hannoun</name>
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<author><name sortKey="Kindler, E" uniqKey="Kindler E">E. Kindler</name>
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<author><name sortKey="Muth, D" uniqKey="Muth D">D. Muth</name>
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<author><name sortKey="Kint, J" uniqKey="Kint J">J. Kint</name>
</author>
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</author>
<author><name sortKey="Drosten, C" uniqKey="Drosten C">C. Drosten</name>
</author>
<author><name sortKey="Thiel, V" uniqKey="Thiel V">V. Thiel</name>
</author>
<author><name sortKey="Trybala, E" uniqKey="Trybala E">E. Trybala</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Madhugiri, R" uniqKey="Madhugiri R">R. Madhugiri</name>
</author>
<author><name sortKey="Fricke, M" uniqKey="Fricke M">M. Fricke</name>
</author>
<author><name sortKey="Marz, M" uniqKey="Marz M">M. Marz</name>
</author>
<author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Muller, C" uniqKey="Muller C">C. Müller</name>
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<author><name sortKey="Karl, N" uniqKey="Karl N">N. Karl</name>
</author>
<author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name>
</author>
<author><name sortKey="Pleschka, S" uniqKey="Pleschka S">S. Pleschka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pan, L" uniqKey="Pan L">L. Pan</name>
</author>
<author><name sortKey="Woodard, J L" uniqKey="Woodard J">J.L. Woodard</name>
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<author><name sortKey="Lucas, D M" uniqKey="Lucas D">D.M. Lucas</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Patton, J T" uniqKey="Patton J">J.T. Patton</name>
</author>
<author><name sortKey="Lustberg, M E" uniqKey="Lustberg M">M.E. Lustberg</name>
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<author><name sortKey="Lozanski, G" uniqKey="Lozanski G">G. Lozanski</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pelletier, J" uniqKey="Pelletier J">J. Pelletier</name>
</author>
<author><name sortKey="Graff, J" uniqKey="Graff J">J. Graff</name>
</author>
<author><name sortKey="Ruggero, D" uniqKey="Ruggero D">D. Ruggero</name>
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<author><name sortKey="Sonenberg, N" uniqKey="Sonenberg N">N. Sonenberg</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Rubio, C A" uniqKey="Rubio C">C.A. Rubio</name>
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<author><name sortKey="Weisburd, B" uniqKey="Weisburd B">B. Weisburd</name>
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<author><name sortKey="Holderfield, M" uniqKey="Holderfield M">M. Holderfield</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sadlish, H" uniqKey="Sadlish H">H. Sadlish</name>
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<author><name sortKey="Paris, C G" uniqKey="Paris C">C.G. Paris</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Saradhi, U V" uniqKey="Saradhi U">U.V. Saradhi</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schatz, J H" uniqKey="Schatz J">J.H. Schatz</name>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schlereth, J" uniqKey="Schlereth J">J. Schlereth</name>
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</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Su, B N" uniqKey="Su B">B.N. Su</name>
</author>
<author><name sortKey="Chai, H" uniqKey="Chai H">H. Chai</name>
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<author><name sortKey="Mi, Q" uniqKey="Mi Q">Q. Mi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Thompson, S R" uniqKey="Thompson S">S.R. Thompson</name>
</author>
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</biblStruct>
<biblStruct><analytic><author><name sortKey="Weik, M" uniqKey="Weik M">M. Weik</name>
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<biblStruct><analytic><author><name sortKey="Zhu, J Y" uniqKey="Zhu J">J.Y. Zhu</name>
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<author><name sortKey="Lavrik, I N" uniqKey="Lavrik I">I.N. Lavrik</name>
</author>
<author><name sortKey="Mahlknecht, U" uniqKey="Mahlknecht U">U. Mahlknecht</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name>
</author>
<author><name sortKey="Siddell, S G" uniqKey="Siddell S">S.G. Siddell</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Allemagne</li>
</country>
<region><li>District de Giessen</li>
<li>Hesse (Land)</li>
</region>
<settlement><li>Marbourg</li>
</settlement>
</list>
<tree><country name="Allemagne"><noRegion><name sortKey="Muller, Christin" sort="Muller, Christin" uniqKey="Muller C" first="Christin" last="Müller">Christin Müller</name>
</noRegion>
<name sortKey="Grunweller, Arnold" sort="Grunweller, Arnold" uniqKey="Grunweller A" first="Arnold" last="Grünweller">Arnold Grünweller</name>
<name sortKey="Hartmann, Roland K" sort="Hartmann, Roland K" uniqKey="Hartmann R" first="Roland K." last="Hartmann">Roland K. Hartmann</name>
<name sortKey="Lange Grunweller, Kerstin" sort="Lange Grunweller, Kerstin" uniqKey="Lange Grunweller K" first="Kerstin" last="Lange-Grünweller">Kerstin Lange-Grünweller</name>
<name sortKey="Madhugiri, Ramakanth" sort="Madhugiri, Ramakanth" uniqKey="Madhugiri R" first="Ramakanth" last="Madhugiri">Ramakanth Madhugiri</name>
<name sortKey="Muller, Christin" sort="Muller, Christin" uniqKey="Muller C" first="Christin" last="Müller">Christin Müller</name>
<name sortKey="Obermann, Wiebke" sort="Obermann, Wiebke" uniqKey="Obermann W" first="Wiebke" last="Obermann">Wiebke Obermann</name>
<name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name>
<name sortKey="Pleschka, Stephan" sort="Pleschka, Stephan" uniqKey="Pleschka S" first="Stephan" last="Pleschka">Stephan Pleschka</name>
<name sortKey="Schulte, Falk W" sort="Schulte, Falk W" uniqKey="Schulte F" first="Falk W." last="Schulte">Falk W. Schulte</name>
<name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
<name sortKey="Ziebuhr, John" sort="Ziebuhr, John" uniqKey="Ziebuhr J" first="John" last="Ziebuhr">John Ziebuhr</name>
</country>
</tree>
</affiliations>
</record>

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Serveur d'exploration MERS

Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

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