Marcos Bryan Heinemann

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Abstract Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin’s efficacy against SARS-CoV-2.

1. Introduction Leptospira spp. are Gram-negative spirochetes that cause leptospirosis and can infect various mammalian host species, including horses and humans. Bacteria can be transmitted indirectly through exposure to polluted water or soil, or directly through contact with animal urine [1].