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Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses.
Barton, Christopher; Kouokam, J Calvin; Hurst, Harrell; Palmer, Kenneth E.
Afiliación
  • Barton C; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. christopher.barton@louisville.edu.
  • Kouokam JC; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. j0kouo01@louisville.edu.
  • Hurst H; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. hehurs01@louisville.edu.
  • Palmer KE; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA. kenneth.palmer@louisville.edu.
Viruses ; 8(12)2016 12 17.
Article en En | MEDLINE | ID: mdl-27999325
Griffithsin (GRFT) is a red alga-derived lectin with demonstrated broad spectrum antiviral activity against enveloped viruses, including severe acute respiratory syndrome-Coronavirus (SARS-CoV), Japanese encephalitis virus (JEV), hepatitis C virus (HCV), and herpes simplex virus-2 (HSV-2). However, its pharmacokinetic profile remains largely undefined. Here, Sprague Dawley rats were administered a single dose of GRFT at 10 or 20 mg/kg by intravenous, oral, and subcutaneous routes, respectively, and serum GRFT levels were measured at select time points. In addition, the potential for systemic accumulation after oral dosing was assessed in rats after 10 daily treatments with GRFT (20 or 40 mg/kg). We found that parenterally-administered GRFT in rats displayed a complex elimination profile, which varied according to administration routes. However, GRFT was not orally bioavailable, even after chronic treatment. Nonetheless, active GRFT capable of neutralizing HIV-Env pseudoviruses was detected in rat fecal extracts after chronic oral dosing. These findings support further evaluation of GRFT for pre-exposure prophylaxis against emerging epidemics for which specific therapeutics are not available, including systemic and enteric infections caused by susceptible enveloped viruses. In addition, GRFT should be considered for antiviral therapy and the prevention of rectal transmission of HIV-1 and other susceptible viruses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Lectinas de Plantas / Suero Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Viruses Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Lectinas de Plantas / Suero Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Viruses Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza