Novel Antiviral Molecules against Ebola Virus Infection
Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I<su...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/19/14791 |
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| author | Mila Collados Rodríguez Patrick Maillard Alexandra Journeaux Anastassia V. Komarova Valérie Najburg Raul-Yusef Sanchez David Olivier Helynck Mingzhe Guo Jin Zhong Sylvain Baize Frédéric Tangy Yves Jacob Hélène Munier-Lehmann Eliane F. Meurs |
| author_facet | Mila Collados Rodríguez Patrick Maillard Alexandra Journeaux Anastassia V. Komarova Valérie Najburg Raul-Yusef Sanchez David Olivier Helynck Mingzhe Guo Jin Zhong Sylvain Baize Frédéric Tangy Yves Jacob Hélène Munier-Lehmann Eliane F. Meurs |
| author_sort | Mila Collados Rodríguez |
| collection | DOAJ |
| description | Infection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I<sub>3D</sub> chemical library using a nanoluciferase-based protein complementation assay (NPCA) and isolated two compounds that disrupt the interaction of the EBOV protein fragment VP35IID with the N-terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose that the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, our data support further testing of the compounds in other species, as well as against other negative-sense RNA viruses. |
| first_indexed | 2024-03-09T13:52:22Z |
| format | Article |
| id | doaj.art-bd6f5c67d6b14e3384fb2d576e3412ba |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:52:22Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bd6f5c67d6b14e3384fb2d576e3412ba2023-11-30T20:48:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191479110.3390/ijms241914791Novel Antiviral Molecules against Ebola Virus InfectionMila Collados Rodríguez0Patrick Maillard1Alexandra Journeaux2Anastassia V. Komarova3Valérie Najburg4Raul-Yusef Sanchez David5Olivier Helynck6Mingzhe Guo7Jin Zhong8Sylvain Baize9Frédéric Tangy10Yves Jacob11Hélène Munier-Lehmann12Eliane F. Meurs13School of Infection & Immunity (SII), College of Medical, Veterinary and Life Sciences (MVLS), Sir Michael Stoker Building, MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UKUnité Hépacivirus et Immunité Innée, CNRS, UMR 3569, Département de Virologie, Institut Pasteur, 75015 Paris, FranceUnit of Biology of Emerging Viral Infections, Institut Pasteur, 69007 Lyon, FranceInteractomics, RNA and Immunity Laboratory, Institut Pasteur, 75015 Paris, FranceUnité de Génomique Virale et Vaccination, Institut Pasteur, 75015 Paris, FranceUnité de Génomique Virale et Vaccination, Institut Pasteur, 75015 Paris, FranceUnité de Chimie et Biocatalyse, CNRS, UMR 3523, Institut Pasteur, Université de Paris, 75015 Paris, FranceCAS Key Laboratory of Molecular Virology and Immunology, Unit of Viral Hepatitis, Shanghai Institute of Immunity and Infection, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai 200023, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Unit of Viral Hepatitis, Shanghai Institute of Immunity and Infection, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai 200023, ChinaUnit of Biology of Emerging Viral Infections, Institut Pasteur, 69007 Lyon, FranceUnité de Génomique Virale et Vaccination, Institut Pasteur, 75015 Paris, FranceUniversité Paris Cité, 75013 Paris, FranceUnité de Chimie et Biocatalyse, CNRS, UMR 3523, Institut Pasteur, Université de Paris, 75015 Paris, FranceUnité Hépacivirus et Immunité Innée, CNRS, UMR 3569, Département de Virologie, Institut Pasteur, 75015 Paris, FranceInfection with Ebola virus (EBOV) is responsible for hemorrhagic fever in humans with a high mortality rate. Combined efforts of prevention and therapeutic intervention are required to tackle highly variable RNA viruses, whose infections often lead to outbreaks. Here, we have screened the 2P2I<sub>3D</sub> chemical library using a nanoluciferase-based protein complementation assay (NPCA) and isolated two compounds that disrupt the interaction of the EBOV protein fragment VP35IID with the N-terminus of the dsRNA-binding proteins PKR and PACT, involved in IFN response and/or intrinsic immunity, respectively. The two compounds inhibited EBOV infection in cell culture as well as infection by measles virus (MV) independently of IFN induction. Consequently, we propose that the compounds are antiviral by restoring intrinsic immunity driven by PACT. Given that PACT is highly conserved across mammals, our data support further testing of the compounds in other species, as well as against other negative-sense RNA viruses.https://www.mdpi.com/1422-0067/24/19/14791Ebola virusmeasles virusVP35PKRPACTRIG-I |
| spellingShingle | Mila Collados Rodríguez Patrick Maillard Alexandra Journeaux Anastassia V. Komarova Valérie Najburg Raul-Yusef Sanchez David Olivier Helynck Mingzhe Guo Jin Zhong Sylvain Baize Frédéric Tangy Yves Jacob Hélène Munier-Lehmann Eliane F. Meurs Novel Antiviral Molecules against Ebola Virus Infection International Journal of Molecular Sciences Ebola virus measles virus VP35 PKR PACT RIG-I |
| title | Novel Antiviral Molecules against Ebola Virus Infection |
| title_full | Novel Antiviral Molecules against Ebola Virus Infection |
| title_fullStr | Novel Antiviral Molecules against Ebola Virus Infection |
| title_full_unstemmed | Novel Antiviral Molecules against Ebola Virus Infection |
| title_short | Novel Antiviral Molecules against Ebola Virus Infection |
| title_sort | novel antiviral molecules against ebola virus infection |
| topic | Ebola virus measles virus VP35 PKR PACT RIG-I |
| url | https://www.mdpi.com/1422-0067/24/19/14791 |
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