Copper inhibits the protease from human immunodeficiency virus 1 by both cysteine-dependent and cysteine-independent mechanisms.

Karlström, Anders R.; Levine, Rodney L.

doi:10.1073/pnas.88.13.5552

Cited by 98 publications

(75 citation statements)

References 33 publications

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“…Most reports suggest that virus inactivation is likely to result from the generation of hydrogen peroxide (H 2 O 2 ) and/or reactive oxygen species (ROS) by redox cycling between the different copper species (9,11,16,28,36). These molecules are known to damage critical biological molecules, such as DNA (2,27,34,35), proteins (13,16,17), and phospholipids (23,31,33). Viruses generally consist of nucleic acid (in either single-stranded [ss] or double-stranded [ds] RNA or DNA forms) surrounded by a protein coat.…”

mentioning

confidence: 99%

Differential Bacteriophage Mortality on Exposure to Copper

Dennehy

2011

Appl Environ Microbiol

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Many studies report that copper can be used to control microbial growth, including that of viruses. We determined the rates of copper-mediated inactivation for a wide range of bacteriophages. We used two methods to test the effect of copper on bacteriophage survival. One method involved placing small volumes of bacteriophage lysate on copper and stainless steel coupons. Following exposure, metal coupons were rinsed with lysogeny broth, and the resulting fluid was serially diluted and plated on agar with the corresponding bacterial host. The second method involved adding copper sulfate (CuSO 4 ) to bacteriophage lysates to a final concentration of 5 mM. Aliquots were removed from the mixture, serially diluted, and plated with the appropriate bacterial host. Significant mortality was observed among the double-stranded RNA (dsRNA) bacteriophages ⌽6 and ⌽8, the single-stranded RNA (ssRNA) bacteriophage PP7, the ssDNA bacteriophage ⌽X174, and the dsDNA bacteriophage PM2. However, the dsDNA bacteriophages PRD1, T4, and were relatively unaffected by copper. Interestingly, lipid-containing bacteriophages were most susceptible to copper toxicity. In addition, in the first experimental method, the pattern of bacteriophage ⌽6 survival over time showed a plateau in mortality after lysates dried out. This finding suggests that copper's effect on bacteriophage is mediated by the presence of water.

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confidence: 99%

Differential Bacteriophage Mortality on Exposure to Copper

Dennehy

2011

Appl Environ Microbiol

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“…The highly conserved nature of these residues, along with the information that this residue is expendable for protease activity [19,28], suggests that their presence might be advantageous to the viral life cycle. It is conceivable that these residues serve to prevent the premature activation of protease in the cytoplasm or decrease its activity in cells under oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

HIV-2 protease is inactivated after oxidation at the dimer interface and activity can be partly restored with methionine sulphoxide reductase

Davis

Newcomb

Moskovitz

et al. 2000

Biochemical Journal

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Human immunodeficiency viruses encode a homodimeric protease that is essential for the production of infectious virus. Previous studies have shown that HIV-1 protease is susceptible to oxidative inactivation at the dimer interface at Cys-95, a process that can be reversed both chemically and enzymically. Here we demonstrate a related yet distinct mechanism of reversible inactivation of the HIV-2 protease. Exposure of the HIV-2 protease to H2O2 resulted in conversion of the two methionine residues (Met-76 and Met-95) to methionine sulphoxide as determined by amino acid analysis and mass spectrometry. This oxidation completely inactivated protease activity. However, the activity could be restored (up to 40%) after exposure of the oxidized protease to methionine sulphoxide reductase. This treatment resulted in the reduction of methionine sulphoxide 95 but not methionine sulphoxide 76 to methionine, as determined by peptide mapping/mass spectrometry. We also found that exposure of immature HIV-2 particles to H2O2 led to the inhibition of polyprotein processing in maturing virus particles comparable to that demonstrated for HIV-1 particles. Thus oxidative inactivation of the HIV protease in vitro and in maturing viral particles is not restricted to the type 1 proteases. These studies indicate that two distinct retroviral proteases are susceptible to inactivation after a very minor modification at residue 95 of the dimer interface and suggest that the dimer interface might be a viable target for the development of novel protease inhibitors.

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“…La elaboración de filtros con óxido de cobre ha permitido eliminar en forma eficiente el riesgo de transmisión de VIH a través de fluidos 14 . Los mecanismos involucrados en la actividad antiviral son la inactivación de una enzima proteasa importante para la replicación viral y daño a nivel de la envoltura fosfolipídica [14][15][16] .…”

Section: Actividad Antiviral Del Cobreunclassified

Aplicación de la capacidad bactericida del cobre en la práctica médica

2012

Rev. méd. Chile

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Copper inhibits the protease from human immunodeficiency virus 1 by both cysteine-dependent and cysteine-independent mechanisms.

Cited by 98 publications

References 33 publications

Differential Bacteriophage Mortality on Exposure to Copper

Differential Bacteriophage Mortality on Exposure to Copper

HIV-2 protease is inactivated after oxidation at the dimer interface and activity can be partly restored with methionine sulphoxide reductase

Aplicación de la capacidad bactericida del cobre en la práctica médica

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