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Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses
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Viruses 2016, 8(12), 331; doi:10.3390/v8120331

Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses

1
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA
2
James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA
3
Center for Predictive Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Barry R. O’Keefe
Received: 11 October 2016 / Revised: 13 December 2016 / Accepted: 13 December 2016 / Published: 17 December 2016
(This article belongs to the Special Issue Lectins as Antiviral)
View Full-Text   |   Download PDF [1153 KB, uploaded 17 December 2016]   |  

Abstract

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. View Full-Text
Keywords: Griffithsin; pharmacokinetics; per os; systemic administration; rat model Griffithsin; pharmacokinetics; per os; systemic administration; rat model
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MDPI and ACS Style

Barton, C.; Kouokam, J.C.; Hurst, H.; Palmer, K.E. Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses. Viruses 2016, 8, 331.

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