tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2011 Sep 19. [Epub ahead of print]
Receptor tyrosine kinase inhibitors that block replication of influenza A and other viruses.
Kumar N, Sharma NR, Ly H, Parslow TG, Liang Y.
Source
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Abstract
We have previously reported that two receptor tyrosine kinase inhibitors (RTKIs), called AG879 and tyrphostin A9 (A9), can each block influenza A virus replication in cultured cells. In this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. The EC(50) of each against influenza A was found to be in the high nanomolar range, and the selectivity index (SI = CC(50)/EC(50)) was determined to be >324 for AG879 and 50 for A9, indicating that therapeutically useful concentrations of each drug produce only low levels of cytotoxicity. Each compound showed efficacy against representative laboratory strains of both human influenza A (H1N1 or H3N2) and influenza B viruses. Importantly, no drug-resistant influenza viral strains emerged even after 25 viral passages in the presence of AG879, whereas viruses resistant to amantadine appeared after only 3 passages. AG879 and A9 each also exhibited potent inhibitory activity against a variety of other RNA and DNA viruses, including Sendai virus (Paramyxoviridae), herpes simplex virus (Herpesviridae), mouse hepatitis virus (Coronaviridae), and rhesus rotavirus (Reoviridae), but not against Pichinde virus (Arenaviridae). These results together suggest that RTKIs may be useful as therapeutics against viral pathogens, including but not limited to influenza, due to their high selectivity indices, low frequency of drug-resistance, and broad-spectrum antiviral activities.
PMID:
21930873
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21930873
Receptor tyrosine kinase inhibitors that block replication of influenza A and other viruses.
Kumar N, Sharma NR, Ly H, Parslow TG, Liang Y.
Source
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.
Abstract
We have previously reported that two receptor tyrosine kinase inhibitors (RTKIs), called AG879 and tyrphostin A9 (A9), can each block influenza A virus replication in cultured cells. In this study, we further characterized the in vitro antiviral efficacies and specificities of these agents. The EC(50) of each against influenza A was found to be in the high nanomolar range, and the selectivity index (SI = CC(50)/EC(50)) was determined to be >324 for AG879 and 50 for A9, indicating that therapeutically useful concentrations of each drug produce only low levels of cytotoxicity. Each compound showed efficacy against representative laboratory strains of both human influenza A (H1N1 or H3N2) and influenza B viruses. Importantly, no drug-resistant influenza viral strains emerged even after 25 viral passages in the presence of AG879, whereas viruses resistant to amantadine appeared after only 3 passages. AG879 and A9 each also exhibited potent inhibitory activity against a variety of other RNA and DNA viruses, including Sendai virus (Paramyxoviridae), herpes simplex virus (Herpesviridae), mouse hepatitis virus (Coronaviridae), and rhesus rotavirus (Reoviridae), but not against Pichinde virus (Arenaviridae). These results together suggest that RTKIs may be useful as therapeutics against viral pathogens, including but not limited to influenza, due to their high selectivity indices, low frequency of drug-resistance, and broad-spectrum antiviral activities.
PMID:
21930873
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21930873