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

Kouokam, Joseph Calvin; Lasnik, Amanda B.; Palmer, Kenneth E.

It has been shown that intravaginal 2 mg/kg GRFT can inhibit HSV-2 [9] ; a similar dose would be used for the mucosal prevention of HIV-1. As shown above, GRFT at this dose caused no detectable toxicity in mice after intravaginal treatment. Although it is unlikely for GRFT to be absorbed through mucosal surfaces after intravaginal administration in healthy subjects, it is possible for the drug to get into circulation in individuals suffering from ulcerative STDs. Indeed, it is widely accepted that STDs are an important risk factor for HIV and vice versa [29] [30] [31] . Therefore, we assessed the effects of 2 mg/kg GRFT delivered by intraperitoneal and subcutaneous administrations, respectively. No adverse effects were found in either case. These results confirm that GRFT has an excellent safety profile as a microbicide candidate, as previously shown using different systems [3, 12, 16, 17] . Interestingly, GRFT was recently shown to significantly protect against genital herpes in a mouse model [9] . Meanwhile, a combination of GRFT and carrageenan displayed potent antiviral effects in mice infected with HSV-2 and human papillomavirus (HPV) [32] . These findings support the development of GRFT as a microbicide for the prevention of HIV/AIDS and other susceptible enveloped viruses.