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PDBsum entry 4zro
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Hydrolase/hydrolase inhibitor
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PDB id
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4zro
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References listed in PDB file
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Key reference
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Title
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X-Ray structure and inhibition of the feline infectious peritonitis virus 3c-Like protease: structural implications for drug design.
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Authors
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S.E.St john,
M.D.Therkelsen,
P.R.Nyalapatla,
H.L.Osswald,
A.K.Ghosh,
A.D.Mesecar.
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Ref.
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Bioorg Med Chem Lett, 2015,
25,
5072-5077.
[DOI no: ]
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PubMed id
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Abstract
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Feline infectious peritonitis (FIP) is a deadly disease that effects both
domestic and wild cats and is caused by a mutation in feline coronavirus (FCoV)
that allows the virus to replicate in macrophages. Currently, there are no
treatments or vaccines available for the treatment of FIP even though it kills
approximately 5% of cats in multi-cat households per year. In an effort to
develop small molecule drugs targeting FIP for the treatment of cats, we
screened a small set of designed peptidomimetic inhibitors for inhibition of
FIPV-3CL(pro), identifying two compounds with low to sub-micromolar inhibition,
compound 6 (IC50=0.59±0.06μM) and compound 7 (IC50=1.3±0.1μM). We determined
the first X-ray crystal structure of FIPV-3CL(pro) in complex with the best
inhibitor identified, compound 6, to a resolution of 2.10Å to better understand
the structural basis for inhibitor specificity. Our study provides important
insights into the structural requirements for the inhibition of FIPV-3CL(pro) by
peptidomimetic inhibitors and expands the current structural knowledge of
coronaviral 3CL(pro) architecture.
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