Snake venom‐derived bradykinin‐potentiating peptides: A promising therapy for COVID‐19?

Gouda, Ahmed S.; Mégarbane, Bruno

The severe acute respiratory syndrome coronavirus‐2 (SARS‐COV‐2), a novel coronavirus responsible for the recent infectious pandemic, is known to downregulate angiotensin‐converting enzyme‐2 (ACE2). Most current investigations focused on SARS‐COV‐2‐related effects on the renin–angiotensin system and especially the resultant increase in angiotensin II, neglecting its effects on the kinin–kallikrein system. SARS‐COV‐2‐induced ACE2 inhibition leads to the augmentation of bradykinin 1‐receptor effects, as ACE2 inactivates des‐Arg9‐bradykinin, a bradykinin metabolite. SARS‐COV‐2 also decreases bradykinin 2‐receptor effects as it affects bradykinin synthesis by inhibiting cathepsin L, a kininogenase present at the site of infection and involved in bradykinin production. The physiologies of both the renin–angiotensin and kinin–kallikrein system are functionally related suggesting that any intervention aiming to treat SARS‐COV‐2‐infected patients by triggering one system but ignoring the other may not be adequately effective. Interestingly, the snake‐derived bradykinin‐potentiating peptide (BPP‐10c) acts on both systems. BPP‐10c strongly decreases angiotensin II by inhibiting ACE, increasing bradykinin‐related effects on the bradykinin 2‐receptor and increasing nitric oxide‐mediated effects. Based on a narrative review of the literature, we suggest that BPP‐10c could be an optimally effective option to consider when aiming at developing an anti‐SARS‐COV‐2 drug.