tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2012 Nov 5. [Epub ahead of print]
Targeting the Organic Anion Transporter-3 (OAT3) with Probenecid as a Novel Anti-Influenza A Virus Strategy.
Perwitasari O, Yan X, Johnson S, White C, Brooks P, Tompkins SM, Tripp RA.
Source
University of Georgia, College of Veterinary Medicine, Dept. Infectious Diseases, 111 Carlton Street, Athens, GA 30302.
Abstract
Influenza A virus infection is a major global health concern causing significant mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target influenza A virus are available; however, rapid emergence of drug resistant strains has been reported. Consequently, there is a burgeoning need to identify novel anti-influenza A drugs, particularly those that target host gene products required for virus replication to reduce the likelihood of drug resistance. In this study, a small interfering RNA (siRNA) screen was performed to identify host druggable gene targets for anti-influenza A virus therapy. The host organic anion transporter-3 gene (OAT3), a member of the SLC22 family of transporters, was validated as being required to support influenza A virus replication. Probenecid, a prototypical uricosuric agent and chemical inhibitor of organic anion transporters was identified to target OAT3, and shown to be effective in limiting influenza A virus infection in vitro (IC(50) of 5.0?10(-5) to 5.0?10(-4) μM; p<0.005) and in vivo (p<0.05). Probenecid is widely used for treatment of gout and related hyperuricemic disorders, has been extensively studied for pharmacokinetics and safety, and represents an excellent candidate for drug repositioning as a novel anti-influenza A chemotherapeutic.
PMID:
23129053
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23129053
Targeting the Organic Anion Transporter-3 (OAT3) with Probenecid as a Novel Anti-Influenza A Virus Strategy.
Perwitasari O, Yan X, Johnson S, White C, Brooks P, Tompkins SM, Tripp RA.
Source
University of Georgia, College of Veterinary Medicine, Dept. Infectious Diseases, 111 Carlton Street, Athens, GA 30302.
Abstract
Influenza A virus infection is a major global health concern causing significant mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target influenza A virus are available; however, rapid emergence of drug resistant strains has been reported. Consequently, there is a burgeoning need to identify novel anti-influenza A drugs, particularly those that target host gene products required for virus replication to reduce the likelihood of drug resistance. In this study, a small interfering RNA (siRNA) screen was performed to identify host druggable gene targets for anti-influenza A virus therapy. The host organic anion transporter-3 gene (OAT3), a member of the SLC22 family of transporters, was validated as being required to support influenza A virus replication. Probenecid, a prototypical uricosuric agent and chemical inhibitor of organic anion transporters was identified to target OAT3, and shown to be effective in limiting influenza A virus infection in vitro (IC(50) of 5.0?10(-5) to 5.0?10(-4) μM; p<0.005) and in vivo (p<0.05). Probenecid is widely used for treatment of gout and related hyperuricemic disorders, has been extensively studied for pharmacokinetics and safety, and represents an excellent candidate for drug repositioning as a novel anti-influenza A chemotherapeutic.
PMID:
23129053
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23129053