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.

Next, we conducted blood chemistry studies and observed no difference due to chronic treatment with GRFT in nearly all parameters, including Alb, BUN, CREAT, TBILI, ALT, AMS, BG, GLOB, TP, Ca, P and Na ( Table 1) . As observed with the single dose of 50 mg/kg GRFT, Chol levels were elevated, reaching 118.75 ± 10.53 mg/dL at Day 14 (control PBS = 87.25 ± 5.37 mg/dL, p = 0.0018); after a week of recovery there was a sharp decrease of cholesterol levels in GRFT-treated animals, although the difference was still statistically significant compared with the control group (Table 1 ). In addition, ALP levels were increased as a consequence of GRFT treatment (159.9% ± 31.0% relative to the PBS treatment group set to 100%) as evaluated at Day 14; at Day 21, there was a slight decrease, but these levels remained higher in the GRFT group (Table 1) . CBC data revealed only minimal treatment-related differences between the GRFT and control groups. The values obtained for red blood cells (total count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cell hemoglobin, mean cell hemoglobin concentration, and red cell distribution width) and platelets (total count and mean platelet volume) were similar in both treatment groups at all time-points (Table 2 ). There was no noticeable difference in the total leukocyte count due to GRFT treatment. However, we observed an increase in neutrophil numbers at Day 14 in the GRFT group (2.7 ± 0.2 vs. 1.7 ± 0.6 in the PBS control group). Nevertheless, this difference was not statistically significant as assessed by a two-tailed unpaired t-test with Welch's correction. Meanwhile, a decrease in lymphocyte numbers was noticed in the GRFT group (3.6 ± 0.4 vs. 5.4 ± 0.7 in controls) but both values fell within the expected range described for mice. As shown in Table 2 , MO, EO, and BA numbers were unchanged. Notably, the hematological profiles of animals seven days post-treatment were similar in both GRFT and PBS groups. Taken together, these findings indicated a good safety profile for GRFT in the murine model after parenteral administration.