Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats
Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved dr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Virus Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0168170223002101 |
| _version_ | 1797631060828225536 |
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| author | Eiichi Hondo Tetsufumi Katta Ayato Sato Naoya Kadofusa Tomoki Ishibashi Hiroshi Shimoda Hirokazu Katoh Atsuo Iida |
| author_facet | Eiichi Hondo Tetsufumi Katta Ayato Sato Naoya Kadofusa Tomoki Ishibashi Hiroshi Shimoda Hirokazu Katoh Atsuo Iida |
| author_sort | Eiichi Hondo |
| collection | DOAJ |
| description | Bat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV. Secondly, the antiviral effects of micafungin on PRV infected human cell lines (HEK293T and A549), and their transcriptome changes by PRV infection were investigated, compared to four different bat-derived cell lines (FBKT1 (Ryukyu flying fox), DEMKT1 (Leschenault's rousette), BKT1 (Greater horseshoe bat), YUBFKT1 (Eastern bent-wing bats)). In two human cell lines, unlike bat cells that induce an IFN-γ response pathway, an endoplasmic reticulum stress response pathway was commonly activated. Additionally, micafungin inhibits viral release rather than suppressing PRV genome replication in human cells, although it was disturbed in Vero cells. The target of micafungin's action may vary depending on the animal species, but it must be useful for human purposes as a first choice of medical care. |
| first_indexed | 2024-03-11T11:15:41Z |
| format | Article |
| id | doaj.art-a3d78eadad6d41f79d9830db917bf1b3 |
| institution | Directory Open Access Journal |
| issn | 1872-7492 |
| language | English |
| last_indexed | 2024-03-11T11:15:41Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Virus Research |
| spelling | doaj.art-a3d78eadad6d41f79d9830db917bf1b32023-11-11T04:27:39ZengElsevierVirus Research1872-74922024-01-01339199248Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by batsEiichi Hondo0Tetsufumi Katta1Ayato Sato2Naoya Kadofusa3Tomoki Ishibashi4Hiroshi Shimoda5Hirokazu Katoh6Atsuo Iida7Laboratory of Animal Morphology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan; Corresponding author at: Laboratory of Animal Morphology, Nagoya University, Nagoya 464-8601, Japan.Laboratory of Animal Morphology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, JapanInstitute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Nagoya 464-8601, JapanInstitute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Nagoya 464-8601, JapanLaboratory for Physical Biology, RIKEN Center for Biosystems Dynamics Research, Kobe 650-0047, JapanLaboratory of Veterinary Microbiology, Joint Graduate School of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, 753-8515, JapanDepartment of Virology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8558, JapanLaboratory of Animal Morphology, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, JapanBat-borne emerging zoonotic viruses cause major outbreaks, such as the Ebola virus, Nipah virus, and/or beta coronavirus. Pteropine orthoreovirus (PRV), whose spillover event occurred from fruits bats to humans, causes respiratory syndrome in humans widely in South East Asia. Repurposing approved drugs against PRV is an effective tool to confront future PRV pandemics. We screened 2,943 compounds in an FDA-approved drug library and identified eight hit compounds that reduce viral cytopathic effects on cultured Vero cells. Real-time quantitative PCR analysis revealed that six of eight hit compounds significantly inhibited PRV replication. Among them, micafungin used clinically as an antifungal drug, displayed a prominent antiviral effect on PRV. Secondly, the antiviral effects of micafungin on PRV infected human cell lines (HEK293T and A549), and their transcriptome changes by PRV infection were investigated, compared to four different bat-derived cell lines (FBKT1 (Ryukyu flying fox), DEMKT1 (Leschenault's rousette), BKT1 (Greater horseshoe bat), YUBFKT1 (Eastern bent-wing bats)). In two human cell lines, unlike bat cells that induce an IFN-γ response pathway, an endoplasmic reticulum stress response pathway was commonly activated. Additionally, micafungin inhibits viral release rather than suppressing PRV genome replication in human cells, although it was disturbed in Vero cells. The target of micafungin's action may vary depending on the animal species, but it must be useful for human purposes as a first choice of medical care.http://www.sciencedirect.com/science/article/pii/S0168170223002101Pteropine orthoreovirusAntiviralFda-approved drugMicafungin |
| spellingShingle | Eiichi Hondo Tetsufumi Katta Ayato Sato Naoya Kadofusa Tomoki Ishibashi Hiroshi Shimoda Hirokazu Katoh Atsuo Iida Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats Virus Research Pteropine orthoreovirus Antiviral Fda-approved drug Micafungin |
| title | Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats |
| title_full | Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats |
| title_fullStr | Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats |
| title_full_unstemmed | Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats |
| title_short | Antiviral effects of micafungin against pteropine orthoreovirus, an emerging zoonotic virus carried by bats |
| title_sort | antiviral effects of micafungin against pteropine orthoreovirus an emerging zoonotic virus carried by bats |
| topic | Pteropine orthoreovirus Antiviral Fda-approved drug Micafungin |
| url | http://www.sciencedirect.com/science/article/pii/S0168170223002101 |
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