Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus
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The activity of inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors, mizoribine and ribavirin, against severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was determined by plaque reduction and yield reduction assays. Mizoribine and ribavirin selectively inhibited replication of SARS-CoV. The 50% inhibitory concentration (IC50) of mizoribine for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, as determined by plaque reduction was 3.5 microg/ml and 16 microg/ml, respectively, and the IC50 of ribavirin for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849 was 20 microg/ml and 80 microg/ml, while the 50% cytotoxic concentration of mizoribine and ribavirin for Vero E6 cells exceeded 200 microg/ml. In a yield reduction assay, mizoribine (10 microg/ml) and ribavirin (40 microg/ml) inhibited the replication of SARS-CoV and reduced the infectious SARS-CoV titers to one-tenth or less. Mizoribine inhibited replication of SARS-CoV more strongly than ribavirin. However, neither drug could completely inhibit replication of SARS-CoV even at concentrations up to 100 microg/ml.
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Host vesicular trafficking, translation, RNA splicing, nucleotide synthesis and glycolysis pathway proteins were upregulated following infection, and targeting these processes with inhibitors revealed potential therapeutic targets.
“Consistently, host vesicular trafficking, translation, RNA splicing, nucleotide synthesis and glycolysis pathway proteins were upregulated following infection143,144 and targeting these processes with inhibitors revealed potential therapeutic targets158,159.”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [158]
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- Authors
- SAIJO, M., MORIKAWA, S., FUKUSHI, S., MIZUTANI, T., HASEGAWA, H., NAGATA, N., IWATA, N., & KURANE, I.
- Affiliations
- National Institute of Infectious Diseases (JP)
- Corresponding author
- SAIJO, M
- Venue
- Antiviral Research
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 66
- Issue
- 2-3
- Pages
- 159-163
- ISSN
- 0166-3542 (ISSN-L)
- PMC
- PMC7114120
- OpenAlex
- W2040236561
- Cited by
- 82
- References
- 33
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 9 · 2021: 15 · 2020: 21 · 2019: 3 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 3 · 2012: 1
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antiviral Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- mizoribine, ribavirin, SARS-CoV, antiviral activity, viral replication inhibition, plaque reduction assay, cytotoxicity
- MeSH terms
- Animals, Antiviral Agents, Chlorocebus aethiops, Microbial Sensitivity Tests, Ribavirin, Ribonucleosides, Vero Cells, Virus Replication, Severe acute respiratory syndrome-related coronavirus
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