Date on Master's Thesis/Doctoral Dissertation

8-2014

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Pharmacology and Toxicology

Committee Chair

Palmer, Kenneth Edward

Committee Member

Chaires, J. Brad

Committee Member

Chen, Theresa

Committee Member

Hurst, Harrell

Committee Member

Matoba, Nobuyuki

Subject

Lectins; Antiviral agents

Abstract

Carbohydrate binding agents that target viral envelope glycans are being studied for their potential use as microbicides and antiviral therapeutics. Griffithsin is a lectin originally identified in a red alga Griffithisia sp. Multiple studies have shown that GRFT inhibits HIV-1, Coronaviruses, Hepatitis C, influenza and Ebola virus replication in vitro. This antiviral activity suggests potential uses in chemoprophylaxis and disease treatment. However, safety of GRFT administration has not been extensively studied. In vivo testing--chronic subcutaneous treatment as well as single dose subcutaneous, oral, and intravenous administrations of Griffithsin in Sprague Dawley Rats (Rattus Norvegicus)--was used to assess Griffithsin’s pharmacokinetic properties and to predict whether use of Griffithsin for antiviral treatment might be safe and effective. Based on histological, serological, and biochemical data derived from these experiments, Griffithsin is generally well tolerated. However, protein binding assays revealed interactions with complement and apolipoproteins and calorimetric assays revealed changes in serum thermograms that may require further study.

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