Inhibition of Cathepsin L: A Possible Mechanism for The Prevention of Ebola Virus Infectivity on The Host Cell

Abstract

Cathepsin L, a lysosomal endopeptidase expressed in most eukaryotic cells, is a member of the papain-like family of cysteine proteinases. This broad-spectrum protease is potent in degrading several extracellular proteins (laminins, fibronectin, collagens I and IV, elastin, and other structural proteins of basement membranes) as well as serum proteins, cytoplasmic and nuclear proteins.
Silibinin is a flavonolignan isolated from milk thistle, Silybum marianum, that has been shown to exhibit antioxidant and antineoplastic activities. The endosomal protease cathepsin L (Cat L) is required for Ebola Virus (EBOV) to enter the cytoplasm and therefore to infect host cells and as such inhibition of the enzyme will possibly prevent or reduce the chances of EBOV infectivity on host cell. This study is therefore aimed on investigating the effect of a possible inhibition of Silibinin on Cathepsin L. In investigating the effects of Silibinin on Cathepsin L activity, different parameters which include the influence of temperature, pH, time and concentrations of substrate on the enzyme in the presence of the inhibitor were studied. This study revealed that the inhibition of cathepsin L activity by silibinin is pH dependent and is favoured in an acidic medium. The highest activity occurred at pH 2.0 while the lowest activity occurred at pH 7.5. Silibinin caused an inhibition at different temperature with maximum inhibition observed at 37 0 C. The result of this study also revealed a time-dependent inhibition of Cathepsin L activity by Silibinin. The significant reduction in the activity of Cathepsin L activity in the presence of Silibinin observed in this study shows that Silibinin is a potent inhibitor of the enzyme. The maximum percentage inhibition achieved for Silibinin was 76% at 1.2Mm. The half maximum inhibitory concentration (IC50) was observed at 0.6mM concentration. This study revealed that Silibinin is a potent inhibitor of Cathepsin L activity as demonstrated in this study and may possibly prevent Ebola virus infectivity on host cell.