Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection.
Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response s...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0316952 |
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| author | Bryce M Warner Robert Vendramelli Amrit S Boese Jonathan Audet Nikesh Tailor Courtney Meilleur Nathan Glowach Marnie Willman Thang Truong Estella Moffat Kevin Tierney Beata Kosak Irfan Dhanidina Jarret Engstrom Bozena Korczak Ian McGowan Carissa Embury-Hyatt Darwyn Kobasa |
| author_facet | Bryce M Warner Robert Vendramelli Amrit S Boese Jonathan Audet Nikesh Tailor Courtney Meilleur Nathan Glowach Marnie Willman Thang Truong Estella Moffat Kevin Tierney Beata Kosak Irfan Dhanidina Jarret Engstrom Bozena Korczak Ian McGowan Carissa Embury-Hyatt Darwyn Kobasa |
| author_sort | Bryce M Warner |
| collection | DOAJ |
| description | Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response seen in severe COVID-19 patients, but there remains an urgent need for development of additional therapeutic options for COVID-19 treatment. A potential drug target is the CCR5-CCL5 axis, and blocking this pathway may protect against severe disease. Here we evaluated whether OB-002, an analog of human CCL5 and a potent antagonist of CCR5, provides therapeutic benefit in SARS-CoV-2 infected Syrian hamsters. Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model. |
| format | Article |
| id | doaj-art-df5cb595735d4c87b6466ca5d2329264 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-df5cb595735d4c87b6466ca5d23292642025-02-10T05:30:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01202e031695210.1371/journal.pone.0316952Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection.Bryce M WarnerRobert VendramelliAmrit S BoeseJonathan AudetNikesh TailorCourtney MeilleurNathan GlowachMarnie WillmanThang TruongEstella MoffatKevin TierneyBeata KosakIrfan DhanidinaJarret EngstromBozena KorczakIan McGowanCarissa Embury-HyattDarwyn KobasaSince the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response seen in severe COVID-19 patients, but there remains an urgent need for development of additional therapeutic options for COVID-19 treatment. A potential drug target is the CCR5-CCL5 axis, and blocking this pathway may protect against severe disease. Here we evaluated whether OB-002, an analog of human CCL5 and a potent antagonist of CCR5, provides therapeutic benefit in SARS-CoV-2 infected Syrian hamsters. Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model.https://doi.org/10.1371/journal.pone.0316952 |
| spellingShingle | Bryce M Warner Robert Vendramelli Amrit S Boese Jonathan Audet Nikesh Tailor Courtney Meilleur Nathan Glowach Marnie Willman Thang Truong Estella Moffat Kevin Tierney Beata Kosak Irfan Dhanidina Jarret Engstrom Bozena Korczak Ian McGowan Carissa Embury-Hyatt Darwyn Kobasa Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. PLoS ONE |
| title | Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. |
| title_full | Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. |
| title_fullStr | Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. |
| title_full_unstemmed | Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. |
| title_short | Treatment with the CCR5 antagonist OB-002 reduces lung pathology, but does not prevent disease in a Syrian hamster model of SARS-CoV-2 infection. |
| title_sort | treatment with the ccr5 antagonist ob 002 reduces lung pathology but does not prevent disease in a syrian hamster model of sars cov 2 infection |
| url | https://doi.org/10.1371/journal.pone.0316952 |
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