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Respiratory syncytial virus infection in macaques is not suppressed by intranasal sprays of pyrimidine biosynthesis inhibitors.
- Source :
-
Antiviral research [Antiviral Res] 2016 Jan; Vol. 125, pp. 58-62. Date of Electronic Publication: 2015 Nov 22. - Publication Year :
- 2016
-
Abstract
- There is imperious need for efficient therapies against ubiquitous and life-threatening respiratory viruses, foremost among them being the human respiratory syncytial virus (hRSV). Several research groups who performed functional screens for broad-spectrum antivirals identified compounds targeting the de novo pyrimidine biosynthesis pathway. Despite their strong antiviral activity in vitro, whether such antimetabolites are effective in vivo remains highly controversial. Here, we evaluated two potent pyrimidine biosynthesis inhibitors developed in our laboratory, IPPA17-A04 and GAC50, in a model of mild hRSV-infection in cynomolgus macaques. In this model, hRSV replication is restricted to the epithelium of the upper respiratory tract, and is compatible with a topical treatment by intranasal sprays. The local administration of palivizumab, a neutralizing anti-hRSV antibody used in clinics, significantly reduced virus replication. In contrast, pyrimidine biosynthesis inhibitors did not show any inhibitory effect on hRSV growth when delivered topically as experimented in our model. Our results should help to better define the potential applications of this class of antimetabolites in the treatment of viral infections.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Intranasal
Animals
Antimetabolites pharmacology
Dihydroorotate Dehydrogenase
Disease Models, Animal
Hep G2 Cells
Humans
Macaca
Oxidoreductases Acting on CH-CH Group Donors antagonists & inhibitors
Palivizumab pharmacology
Pyrimidines biosynthesis
Respiratory Syncytial Virus Infections metabolism
Respiratory Syncytial Virus Infections virology
Respiratory Syncytial Virus, Human growth & development
Respiratory Syncytial Virus, Human physiology
Virus Replication drug effects
Antiviral Agents pharmacology
Pyrimidines antagonists & inhibitors
Respiratory Syncytial Virus Infections drug therapy
Respiratory Syncytial Virus, Human drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9096
- Volume :
- 125
- Database :
- MEDLINE
- Journal :
- Antiviral research
- Publication Type :
- Academic Journal
- Accession number :
- 26593978
- Full Text :
- https://doi.org/10.1016/j.antiviral.2015.11.006