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

Shen, Zu T.; Sigalov, Alexander B.

In summary, the data presented in this study provide the first experimental evidence of the previously predicted immunomodulatory activity of SARS CoV FP 29 and demonstrate a strong anti-arthritic effect of the SARS CoV FP-derived 11 amino acid-long peptide sequence in a mouse model of RA. Interestingly, immunosuppressive activity of the influenza FP has been recently demonstrated in vitro 59 . Further, we suggested before that: 1) short synthetic peptides (SCHOOL peptides) can be designed in line with the SCHOOL platform-based strategy for therapeutic inhibition and modulation of a variety of functionally unrelated multichain receptors expressed on various cells, and 2) the molecular mechanisms of action of the SCHOOL peptides is similar to those that viruses use to evade the immune system 26, 43, 44 . To date, the SCHOOL peptides that target TREM-1, glycoprotein receptor VI (GPVI), and TCR were demonstrated both in vitro and in vivo to represent promising therapeutic approaches to the treatment of a variety of diseases with unmet clinical need including sepsis, lung cancer, rheumatoid arthritis, dermatoses, and others [33] [34] 52, 58, 60 . Taken together, these findings further support our unifying hypothesis 29, 44 that the viral immune evasion strategies developed and optimized during millions of years of evolution of virus-host interactions can be practically used for the rational drug design of new mechanism-based therapies. incubated at 50 °C for 30 min. After cooling to 30 °C, the solution containing a 1:1 mixture of apo A-I peptides H4 and H6 in PBS, pH 7.4 was added and the mixture was incubated at 30 °C for 3 h, followed by extensive dialysis against PBS to remove sodium cholate. The obtained MG11-sHDL particles were then purified on a calibrated Superdex 200HR gel filtration column (GE Healthcare Biosciences, Pittsburgh, PA) using the BioCAD 700E Workstation (Applied Biosystems, Carlsbad, CA) and characterized by analytical RP-HPLC and nondenaturing gel electrophoresis as described previously 33 . Final peptide compositions were determined in the prepared particles by analytical RP-HPLC as previously described 33 . The mean size of the particles was determined using electron microscopy as described 33 . Animal studies. Animal studies were performed by Bolder BioPATH (Boulder, CO). All animal experiments were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH) and in the United States Department of Agriculture (USDA) Animal Welfare Act (9 CFR, Parts 1, 2, and 3). The protocol (BBP-001.B) was approved by the Institutional Animal Care and Use Committee (IACUC) of Bolder BioPATH for compliance with regulations prior to study initiation (Animal Welfare Assurance number A7649-06) and all methods were performed in accordance with the approved protocol.