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GC376 is an inhibitor of 3C- and 3C-like proteases.1 It inhibits recombinant poliovirus, foot and mouth disease virus (FMDV), and human rhinovirus (HRV) 3C proteases (IC50s = 1.77, 1.16, and 0.2 μM, respectively). GC376 also inhibits recombinant Norwalk virus, MD145 virus, transmissible gastroenteritis virus (TGEV), and severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like proteases (IC50s = 0.49, 0.96, 0.82 and 4.35 μM, respectively). It reduces the cytopathic effect of SARS-CoV-2 in infected Vero E6 cells (EC50 = 3.37 μM).2 GC376 also reduces liver viral titers by 9.86- and 21.99-fold in a model of murine hepatitis virus (MHV A59) infection when administered at doses of 50 and 100 mg/kg per day, respectively.3

1.Kim, Y., Lovell, S., Tiew, K.-C., et al.Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronavirusesJ. Virol.86(21)11754-11762(2012) 2.Ma, C., Sacco, M.D., Hurst, B., et al.Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main proteaseCell Res.30(8)678-692(2020) 3.Kim, Y., Shivanna, V., Narayanan, S., et al.Broad-spectrum inhibitors against 3C-like proteases of feline coronaviruses and feline calicivirusesJ. Virol.89(9)4942-4950(2015)

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