Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool
IntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chi...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2023.1192583/full |
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| author | Towseef Akram Irfan Gul Irfan Gul Mahrukh Parveez Zia Mahrukh Parveez Zia Amreena Hassan Amreena Hassan Amina Khatun Riaz Ahmad Shah Syed Mudasir Ahmad Nazir Ahmad Ganai Naveed Anjum Chikan Won-Il Kim Nadeem Shabir |
| author_facet | Towseef Akram Irfan Gul Irfan Gul Mahrukh Parveez Zia Mahrukh Parveez Zia Amreena Hassan Amreena Hassan Amina Khatun Riaz Ahmad Shah Syed Mudasir Ahmad Nazir Ahmad Ganai Naveed Anjum Chikan Won-Il Kim Nadeem Shabir |
| author_sort | Towseef Akram |
| collection | DOAJ |
| description | IntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent.MethodsThe cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored.Results and DiscussionRibavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme’s active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus. |
| first_indexed | 2024-03-12T20:54:38Z |
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| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-03-12T20:54:38Z |
| publishDate | 2023-07-01 |
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| spelling | doaj.art-df02042bc63d45e3b685d90866deeb9a2023-07-31T21:32:13ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-07-011010.3389/fvets.2023.11925831192583Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine poolTowseef Akram0Irfan Gul1Irfan Gul2Mahrukh Parveez Zia3Mahrukh Parveez Zia4Amreena Hassan5Amreena Hassan6Amina Khatun7Riaz Ahmad Shah8Syed Mudasir Ahmad9Nazir Ahmad Ganai10Naveed Anjum Chikan11Won-Il Kim12Nadeem Shabir13Division of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDepartment of Biotechnology, University of Kashmir, Srinagar, IndiaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDepartment of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, UP, IndiaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDepartment of Biotechnology, University of Kashmir, Srinagar, IndiaFaculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, BangladeshDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaDivision of Computational Biology, Daskdan Innovations Pvt. Ltd., Srinagar, IndiaCollege of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaDivision of Animal Biotechnology, Faculty of Veterinary Sciences and Animal Husbandry, Sher-e- Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, IndiaIntroductionThe antiviral activity of different mutagens against single-stranded RNA viruses is well documented; however, their activity on the replication of double-stranded RNA viruses remains unexplored. This study aims to investigate the effect of different antivirals on the replication of a chicken embryo fibroblast-adapted Infectious Bursal Disease virus, FVSKG2. This study further explores the antiviral mechanism utilized by the most effective anti-IBDV agent.MethodsThe cytotoxicity and anti-FVSKG2 activity of different antiviral agents (ribavirin, 5-fluorouracil, 5-azacytidine, and amiloride) were evaluated. The virus was serially passaged in chicken embryo fibroblasts 11 times at sub-cytotoxic concentrations of ribavirin, 5-fluorouracil or amiloride. Further, the possible mutagenic and non-mutagenic mechanisms utilized by the most effective anti-FVSKG2 agent were explored.Results and DiscussionRibavirin was the least cytotoxic on chicken embryo fibroblasts, followed by 5-fluorouracil, amiloride and 5-azacytidine. Ribavirin inhibited the replication of FVSKG2 in chicken embryo fibroblasts significantly at concentrations as low as 0.05 mM. The extinction of FVSKG2 was achieved during serial passage of the virus in chicken embryo fibroblasts at ≥0.05 mM ribavirin; however, the emergence of a mutagen-resistant virus was not observed until the eleventh passage. Further, no mutation was observed in 1,898 nucleotides of the FVSKG2 following its five passages in chicken embryo fibroblasts in the presence of 0.025 mM ribavirin. Ribavarin inhibited the FVSKG2 replication in chicken embryo fibroblasts primarily through IMPDH-mediated depletion of the Guanosine Triphosphate pool of cells. However, other mechanisms like ribavirin-mediated cytokine induction or possible inhibition of viral RNA-dependent RNA polymerase through its interaction with the enzyme’s active sites enhance the anti-IBDV effect. Ribavirin inhibits ds- RNA viruses, likely through IMPDH inhibition and not mutagenesis. The inhibitory effect may, however, be augmented by other non-mutagenic mechanisms, like induction of antiviral cytokines in chicken embryo fibroblasts or interaction of ribavirin with the active sites of RNA-dependent RNA polymerase of the virus.https://www.frontiersin.org/articles/10.3389/fvets.2023.1192583/fullinfectious bursal disease virusribavirindsRNAantiviralmutagen |
| spellingShingle | Towseef Akram Irfan Gul Irfan Gul Mahrukh Parveez Zia Mahrukh Parveez Zia Amreena Hassan Amreena Hassan Amina Khatun Riaz Ahmad Shah Syed Mudasir Ahmad Nazir Ahmad Ganai Naveed Anjum Chikan Won-Il Kim Nadeem Shabir Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool Frontiers in Veterinary Science infectious bursal disease virus ribavirin dsRNA antiviral mutagen |
| title | Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| title_full | Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| title_fullStr | Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| title_full_unstemmed | Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| title_short | Ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| title_sort | ribavirin inhibits the replication of infectious bursal disease virus predominantly through depletion of cellular guanosine pool |
| topic | infectious bursal disease virus ribavirin dsRNA antiviral mutagen |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2023.1192583/full |
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