Soybean Trypsin Inhibitor Possesses Potency Against SARS-CoV-2 Infection by Blocking the Host Cell Surface Receptors ACE2, TMPRSS2, and CD147

Int J Mol Sci. 2025 Jul 9;26(14):6583. doi: 10.3390/ijms26146583.

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that helps the body regulate blood pressure and endocrine secretions. Transmembrane serine protease 2 (TMPRSS2) is a cell surface protein expressed mainly by endothelial cells of the respiratory and digestive tract, which participates in the cleavage of protein peptide bonds with serine as the active site. These two proteins have been studied to be highly associated with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soybean trypsin inhibitor (SBTI) has special bioactivities such as anticarcinogenic and anti-inflammatory functions, which can be widely used in functional foods or drugs. Our study involved in vitro and in vivo experiments to elucidate the effect of SBTI on SARS-CoV-2 host invasion. First, it was confirmed that being under 250 μg/mL of SBTI was not toxic to HepG2, HEK293T, and Calu-3 cells. The animal study administered SBTI to mice once daily for 14 days. In the lungs, liver, and kidneys, the histopathologic findings of the SBTI group were not different from those of the control group, but the expression of ACE2, TMPRSS2, and CD147 was reduced. Thus, our findings suggest that the inhibition of ACE2, TMPRSS,2 and CD147 proteins by SBTI shows promise in potentially inhibiting SARS-CoV-2 infection.

Keywords: ACE2; CD147; SARS-CoV-2; TMPRSS2; soybean trypsin inhibitor.

MeSH terms

  • Angiotensin-Converting Enzyme 2* / antagonists & inhibitors
  • Angiotensin-Converting Enzyme 2* / metabolism
  • Animals
  • Basigin* / antagonists & inhibitors
  • Basigin* / metabolism
  • COVID-19 / metabolism
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Glycine max / chemistry
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • SARS-CoV-2* / drug effects
  • Serine Endopeptidases* / metabolism
  • Soybean Proteins* / pharmacology
  • Trypsin Inhibitors* / pharmacology
  • Virus Internalization / drug effects

Substances

  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • Basigin
  • ACE2 protein, human
  • Trypsin Inhibitors
  • BSG protein, human
  • Soybean Proteins