Bulk production of the antiviral lectin griffithsin

Fuqua, Joshua L.; Hamorsky, Krystal; Khalsa, Guruatma; Matoba, Nobuyuki; Palmer, Kenneth E.

Griffithsin (GRFT) is a 121 amino acid lectin identified in the red marine alga, Griffithsia sp. (Mori et al., 2005) . Structural characterization of GRFT showed it to be a domain swapped homodimer with six carbohydrate binding sites that bind to terminal mannose residues on N-linked glycans of the HIV envelope protein, gp120 (Moulaei et al., 2010; Xue et al., 2012 Xue et al., , 2013 Ziolkowska et al., 2006) . Subsequent functional characterization of GRFT has demonstrated it to be a potent HIV inhibitor with minimal toxicity in vitro and in vivo (Barton et al., 2014; Emau et al., 2007; Kouokam et al., 2011; Mori et al., 2005; O'Keefe et al., 2009) . GRFT displays picomolar EC 50 values in its inhibition of laboratory and primary HIV-1 and HIV-2 isolates and has shown stability and activity in macaque vaginal fluid (Emau et al., 2007; Ferir et al., 2012; Mori et al., 2005) . Further investigation of GRFT's safety profile revealed that although it can bind the human squamous epithelial layer and peripheral blood mononuclear cells, cells and tissues did not exhibit significant inflammatory responses when exposed to GRFT and GRFT retained picomolar levels of antiviral activity (Kouokam et al., 2011) . Our studies on topical delivery of GRFT in a murine model of SARS-Coronavirus infection showed GRFT treatment to be both safe and efficacious , and studies on systemic delivery of GRFT also showed a good safety profile in rodent models with minimal changes in spleen and liver size and no coincident pathological changes (Barton et al., 2014) . GRFT's favourable safety profile and potent, broad spectrum antiviral activity has promoted its development as an HIV microbicide (Zeitlin et al., 2009) .