Gallinamide A TFA is a linearly depositing peptide and a potent inhibitor of cathepsin L (CatL) (IC50: 17.6 pM). Gallinamide A TFA inhibits SARS-CoV-2 infection by inhibiting CatL (EC50: 28 nM). Gallinamide A TFA also inhibits Plasmodium falciparum (IC50: 50 nM).
Gallinamide A TFA has low cytotoxicity with CC50 >100 μM in VeroE6 cells. Gallinamide A TFA (0.5 μM; 96 h) can inhibit CatL-mediated SARS-CoV-2 endosome entry into VeroE6 cells[1].
Gallinamide A TFA also mesylate with the TMPRSS2 inhibitor Nafamostat exhibits synergistic effects. Potent antiviral activity in HEK-ACE2-TMPRSS2 cells, but ineffective in VeroE6 cell line[1].
References:
[1]. Ashhurst AS, et al. Potent in vitro anti-SARS-CoV-2 activity by gallinamide A and analogues via inhibition of cathepsin L. bioRxiv [Preprint]. 2020 Dec 24:2020.12.23.424111.
[2]. Stoye A, et al. Falcipain Inhibitors Based on the Natural Product Gallinamide A Are Potent in Vitro and in Vivo Antimalarials. J Med Chem. 2019 Jun 13;62(11):5562-5578.