SARS Coronavirus Fusion Peptide-Derived Sequence Suppresses Collagen-Induced Arthritis in DBA/1J Mice

Shen, Zu T.; Sigalov, Alexander B.

Previously, we reported that incorporation of another immunomodulatory peptide, GF9, that employs the SCHOOL mechanisms of action and targets triggering receptor expressed on myeloid cells 1 (TREM-1), into synthetic HDL-like nanoparticles of spherical shape (sHDL) significantly reduces the effective therapeutic dosage of GF9 in animal models of sepsis, lung cancer, and RA 33, 34 . To evaluate whether incorporation of MG11 into sHDL may have a similar effect, sHDL-bound MG11 was i.p. administered daily at a dose of 2.5 mg/kg MG11. Despite a 10-fold decrease in administration dose of MG11, the arthritis inhibitory effect observed for 2.5 mg/kg/day MG11-HDL was comparable to that observed for 25 mg/kg/day peptide in free form (Fig. 2a) . Although the underlying molecular mechanisms of this phenomenon are not completely understood and need to be further investigated, one can suggest that this results from the prolonged circulatory half-life of sHDL-bound MG11: while the in vivo peptide half-life is short, typically a few minutes 35 , sHDL are characterized by much longer half-lives up to 3-5 days 36 .