Comparison of inhibitor binding to feline and human immunodeficiency virus proteases: Structure‐based drug design and the resistance problem

Dunn, Ben M.; Pennington, Michael W.; Frase, D. Constanza; Nash, Kevin

doi:10.1002/(sici)1097-0282(1999)51:1<69::aid-bip8>3.0.co;2-#

Cited by 12 publications

(3 citation statements)

References 19 publications

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“…Similar to SIV and HIV-1 PRs, autoproteolysis of FIV protease is observed in vitro (102). Despite these similarities, FIV PR is specific to its respective substrates and inhibitors of HIV-1 protease currently employed in clinic do not inhibit FIV protease (103–105). FIV protease cleaves the FIV MA/CA cleavage junction efficiently.…”

Section: Introductionmentioning

confidence: 99%

Feline Immunodeficiency Virus (FIV) as A Model for Study of Lentivirus Infections: Parallels with HIV

Elder¹,

Lin²,

Fink³

et al. 2010

CHR

100

114

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FIV is a significant pathogen in the cat and is, in addition, the smallest available natural model for the study of lentivirus infections. Although divergent at the amino acid level, the cat lentivirus has an abundance of structural and pathophysiological commonalities with HIV and thus serves well as a model for development of intervention strategies relevant to infection in both cats and man. The following review highlights both the strengths and shortcomings of the FIV/cat model, particular as regards development of antiviral drugs.

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Section: Introductionmentioning

confidence: 99%

Feline Immunodeficiency Virus (FIV) as A Model for Study of Lentivirus Infections: Parallels with HIV

Elder¹,

Lin²,

Fink³

et al. 2010

CHR

100

114

View full text Add to dashboard Cite

show abstract

“…It has been shown that FIV protease behaves like the drug-resistant phenotypes of HIV protease (DUNN et al, 1999) as several HIV protease amino acid residues mutate to the structurally aligned residue found in FIV protease (SLEE et al, 1995).…”

Section: Efficacy Against Fivmentioning

confidence: 99%

Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells

Schwartz

McCrackin²,

Schinazi³

et al. 2014

ajvr

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“…The fluorogenic FIV CA/NC2 junction substrate that is cleaved efficiently by FIV protease has Val at both P2 and P2Ј. Interestingly, two very potent FIV protease inhibitors, TL-3 and HBY-793, also have Val at P2 and P2Ј (5,21). In addition, FIV protease appears to prefer nonpolar amino acids like Val at P2Ј instead of the charged Glu or polar Gln amino acids readily cleaved by HIV-1 protease (28,40).…”

Section: Vol 74 2000mentioning

confidence: 99%

Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus Protease

Lin¹,

Beck²,

Lee

et al. 2000

J. Virol.

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Feline immunodeficiency virus (FIV) protease is structurally very similar to human immunodeficiency virus (HIV) protease but exhibits distinct substrate and inhibitor specificities. We performed mutagenesis of subsite residues of FIV protease in order to define interactions that dictate this specificity. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. FIV proteases all failed to cut HIV-1 matrix/capsid, P1/P6, P6/protease, and protease/reverse transcriptase junctions, indicating that none of the substitutions were sufficient to change the specificity completely. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. The data also suggest that FIV protease prefers a hydrophobic P2/P2 residue like Val over Asn or Glu, which are utilized by HIV-1 protease, and that S2/S2 might play a critical role in distinguishing FIV and HIV-1 protease by specificity. The findings extend our observations regarding the interactions involved in substrate binding and aid in the development of broad-based inhibitors.

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Comparison of inhibitor binding to feline and human immunodeficiency virus proteases: Structure‐based drug design and the resistance problem

Cited by 12 publications

References 19 publications

Feline Immunodeficiency Virus (FIV) as A Model for Study of Lentivirus Infections: Parallels with HIV

Feline Immunodeficiency Virus (FIV) as A Model for Study of Lentivirus Infections: Parallels with HIV

Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells

Alteration of Substrate and Inhibitor Specificity of Feline Immunodeficiency Virus Protease

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