The new coronavirus (SARS-CoV-2) has spread around the world at an unprecedented rate, circumventing containment countermeasures. Understanding the mechanisms by which SARS-CoV-2 successfully evades the body’s defense systems is essential to reducing the transmission of this virus.
A research group from Osaka Metropolitan University led by Associate Professor Misako Matsubara of the Department of Veterinary Sciences, the Graduate School of Veterinary Sciences and Professor Katsutoshi Yoshizato of the Department of Hepatology, the Graduate School of Veterinary Sciences Medicine, they suspected that the innate immune system could prevent SARS-CoV-2 infection; the onset and severity of new coronavirus infection (COVID-19) depend on age, as well as the volume and quality of saliva, which are significantly reduced in the elderly.
SARS-CoV-2 is transmitted when the S1 tip protein of the viral envelope binds to the angiotensin 2 converting enzyme (ACE2) receptor on the human cell membrane. Saliva and oral cells are important routes of transmission for COVID-19 infection. The research group has shown that the saliva of (healthy) individuals not infected with SARS-CoV-2 interferes with the binding of S1 and ACE2 in a concentration-dependent manner. They identified four proteins in saliva that bind to ACE2 and between these proteins, neutrophil elastase and histone H2A markedly inhibit the binding of S1 and ACE2. Neutrophil elastase and H2A are positively charged proteins, which act as a barrier against SARS-CoV-2 binding by covering the ACE2-negatively charged S1 binding site. The research group also showed that cationic polypeptides such as ε-poly-L-lysine are equally effective in preventing the binding of S1 to ACE2.
This research is the result of a joint study by the Osaka Metropolitan University Graduate School of Medicine and the Graduate School of Veterinary Science, and Cosmo Bio Co., Ltd., and was published online in The Journal of Biochemistry on 6 July 2022.
This study shows that salivary neutrophils are moderately activated by native microorganisms and continuously release a variety of proteins, including elastase and histone H2A contribute to self-defense against SARS-CoV-2 infection by masking the ACE2 receptor a the host cells. We believe that our findings will contribute to the development of methods not only to prevent or treat COVID-19 infection, but also to prevent unknown viruses from infecting humans in the future on an innate immune level. ”
Professor Katsutoshi Yoshizato, Department of Hepatology, Graduate School of Medicine
Source:
Osaka Metropolitan University
Magazine reference:
Yoshizato, K., et al. (2022) Enabling the ACE2 receptor with salivary cathinic proteins inhibits the entry of SARS-CoV-2. Journal of Biochemistry. doi.org/10.1093/jb/mvac054.