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
Viruses 2016, 8(12), 331; https://doi.org/10.3390/v8120331
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)
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
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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. https://doi.org/10.3390/v8120331
AMA Style
Barton C, Kouokam JC, Hurst H, Palmer KE. Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses. Viruses. 2016; 8(12):331. https://doi.org/10.3390/v8120331
Chicago/Turabian StyleBarton, Christopher, J. C. Kouokam, Harrell Hurst, and Kenneth E. Palmer. 2016. "Pharmacokinetics of the Antiviral Lectin Griffithsin Administered by Different Routes Indicates Multiple Potential Uses" Viruses 8, no. 12: 331. https://doi.org/10.3390/v8120331
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
