Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats
The synthetic compounds, Tilorone and Cridanimod, have the antiviral activity which initially had been ascribed to the capacity to induce interferon. Both drugs induce interferon in mice but not in humans. This study investigates whether these compounds have the antiviral activity in mice and rats s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/5/617 |
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| author | Viktoriya Keyer Laura Syzdykova Gulzat Zauatbayeva Aigerim Zhulikeyeva Yerlan Ramanculov Alexandr V. Shustov Zarina Shulgau |
| author_facet | Viktoriya Keyer Laura Syzdykova Gulzat Zauatbayeva Aigerim Zhulikeyeva Yerlan Ramanculov Alexandr V. Shustov Zarina Shulgau |
| author_sort | Viktoriya Keyer |
| collection | DOAJ |
| description | The synthetic compounds, Tilorone and Cridanimod, have the antiviral activity which initially had been ascribed to the capacity to induce interferon. Both drugs induce interferon in mice but not in humans. This study investigates whether these compounds have the antiviral activity in mice and rats since rats more closely resemble the human response. Viral-infection models were created in CD-1 mice and Wistar rats. Three strains of Venezuelan equine encephalitis virus were tested for the performance in these models. One virus strain is the molecularly cloned attenuated vaccine. The second strain has major virulence determinants converted to the wild-type state which are present in virulent strains. The third virus has wild-type virulence determinants, and in addition, is engineered to express green fluorescent protein. Experimentally infected animals received Tilorone or Cridanimod, and their treatment was equivalent to the pharmacopoeia-recomended human treatment regimen. Tilorone and Cridanimod show the antiviral activity in mice and rats and protect the mice from death. In rats, both drugs diminish the viremia. These drugs do not induce interferon-alpha or interferon-beta in rats. The presented observations allow postulating the existence of an interferon-independent and species-independent mechanism of action. |
| first_indexed | 2024-03-10T03:09:30Z |
| format | Article |
| id | doaj.art-73107b99350b4b69bddd4d7a8dfbb37a |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T03:09:30Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-73107b99350b4b69bddd4d7a8dfbb37a2023-11-23T12:35:28ZengMDPI AGPharmaceuticals1424-82472022-05-0115561710.3390/ph15050617Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in RatsViktoriya Keyer0Laura Syzdykova1Gulzat Zauatbayeva2Aigerim Zhulikeyeva3Yerlan Ramanculov4Alexandr V. Shustov5Zarina Shulgau6National Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanNational Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, KazakhstanThe synthetic compounds, Tilorone and Cridanimod, have the antiviral activity which initially had been ascribed to the capacity to induce interferon. Both drugs induce interferon in mice but not in humans. This study investigates whether these compounds have the antiviral activity in mice and rats since rats more closely resemble the human response. Viral-infection models were created in CD-1 mice and Wistar rats. Three strains of Venezuelan equine encephalitis virus were tested for the performance in these models. One virus strain is the molecularly cloned attenuated vaccine. The second strain has major virulence determinants converted to the wild-type state which are present in virulent strains. The third virus has wild-type virulence determinants, and in addition, is engineered to express green fluorescent protein. Experimentally infected animals received Tilorone or Cridanimod, and their treatment was equivalent to the pharmacopoeia-recomended human treatment regimen. Tilorone and Cridanimod show the antiviral activity in mice and rats and protect the mice from death. In rats, both drugs diminish the viremia. These drugs do not induce interferon-alpha or interferon-beta in rats. The presented observations allow postulating the existence of an interferon-independent and species-independent mechanism of action.https://www.mdpi.com/1424-8247/15/5/617TiloroneCridanimodinterferon inducing agentsmall animal modelsVenezuelan equine encephalitis virusantiviral state |
| spellingShingle | Viktoriya Keyer Laura Syzdykova Gulzat Zauatbayeva Aigerim Zhulikeyeva Yerlan Ramanculov Alexandr V. Shustov Zarina Shulgau Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats Pharmaceuticals Tilorone Cridanimod interferon inducing agent small animal models Venezuelan equine encephalitis virus antiviral state |
| title | Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats |
| title_full | Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats |
| title_fullStr | Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats |
| title_full_unstemmed | Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats |
| title_short | Tilorone and Cridanimod Protect Mice and Show Antiviral Activity in Rats despite Absence of the Interferon-Inducing Effect in Rats |
| title_sort | tilorone and cridanimod protect mice and show antiviral activity in rats despite absence of the interferon inducing effect in rats |
| topic | Tilorone Cridanimod interferon inducing agent small animal models Venezuelan equine encephalitis virus antiviral state |
| url | https://www.mdpi.com/1424-8247/15/5/617 |
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