A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures
Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/13/1/52 |
| _version_ | 1797542810805600256 |
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| author | Ryan P. Bennett Courtney L. Finch Elena N. Postnikova Ryan A. Stewart Yingyun Cai Shuiqing Yu Janie Liang Julie Dyall Jason D. Salter Harold C. Smith Jens H. Kuhn |
| author_facet | Ryan P. Bennett Courtney L. Finch Elena N. Postnikova Ryan A. Stewart Yingyun Cai Shuiqing Yu Janie Liang Julie Dyall Jason D. Salter Harold C. Smith Jens H. Kuhn |
| author_sort | Ryan P. Bennett |
| collection | DOAJ |
| description | Filoviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody-based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. Using this assay, we screened nearly 3000 small molecules and identified several molecules with the desired inhibitory properties. In secondary assays, one identified compound, sangivamycin, inhibited not only Ebola viral infectivity but also that of other viruses. This finding indicates that it is possible for this new VP40-based screening method to identify highly potent MCMs against Ebola virus and its relatives. |
| first_indexed | 2024-03-10T13:36:43Z |
| format | Article |
| id | doaj.art-5945a79a982544e080a424c8503cb249 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T13:36:43Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-5945a79a982544e080a424c8503cb2492023-11-21T07:28:41ZengMDPI AGViruses1999-49152020-12-011315210.3390/v13010052A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical CountermeasuresRyan P. Bennett0Courtney L. Finch1Elena N. Postnikova2Ryan A. Stewart3Yingyun Cai4Shuiqing Yu5Janie Liang6Julie Dyall7Jason D. Salter8Harold C. Smith9Jens H. Kuhn10OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USAOyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USAOyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USAOyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USANIH/NIAID/DCR/Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USAFiloviruses, such as Ebola virus and Marburg virus, are of significant human health concern. From 2013 to 2016, Ebola virus caused 11,323 fatalities in Western Africa. Since 2018, two Ebola virus disease outbreaks in the Democratic Republic of the Congo resulted in 2354 fatalities. Although there is progress in medical countermeasure (MCM) development (in particular, vaccines and antibody-based therapeutics), the need for efficacious small-molecule therapeutics remains unmet. Here we describe a novel high-throughput screening assay to identify inhibitors of Ebola virus VP40 matrix protein association with viral particle assembly sites on the interior of the host cell plasma membrane. Using this assay, we screened nearly 3000 small molecules and identified several molecules with the desired inhibitory properties. In secondary assays, one identified compound, sangivamycin, inhibited not only Ebola viral infectivity but also that of other viruses. This finding indicates that it is possible for this new VP40-based screening method to identify highly potent MCMs against Ebola virus and its relatives.https://www.mdpi.com/1999-4915/13/1/52broad spectrumEbola virus<i>Filoviridae</i>filovirusMarburg virusMCM |
| spellingShingle | Ryan P. Bennett Courtney L. Finch Elena N. Postnikova Ryan A. Stewart Yingyun Cai Shuiqing Yu Janie Liang Julie Dyall Jason D. Salter Harold C. Smith Jens H. Kuhn A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures Viruses broad spectrum Ebola virus <i>Filoviridae</i> filovirus Marburg virus MCM |
| title | A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures |
| title_full | A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures |
| title_fullStr | A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures |
| title_full_unstemmed | A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures |
| title_short | A Novel Ebola Virus VP40 Matrix Protein-Based Screening for Identification of Novel Candidate Medical Countermeasures |
| title_sort | novel ebola virus vp40 matrix protein based screening for identification of novel candidate medical countermeasures |
| topic | broad spectrum Ebola virus <i>Filoviridae</i> filovirus Marburg virus MCM |
| url | https://www.mdpi.com/1999-4915/13/1/52 |
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