Essential viral and cellular zinc and iron containing metalloproteins as targets for novel antiviral and anticancer agents: implications for prevention and therapy of viral diseases and cancer.
In this review the authors summarize the experimental data on the role of a selected group of metalloproteins, particularly viral (v) and cellular (c) zinc finger proteins (ZFP) and iron containing proteins which are involved in cell proliferation, neovascularization, apoptosis, and viral infection. Furthermore, this review summarizes the data embracing the hypothesis that disruption of certain metalloproteins by novel pharmacological agents is a key factor in controlling viral and proliferative diseases. The primary goal of this review is to show the potential therapeutic applications of ZFP disrupting agents, zinc chelators and iron chelators in the control of viral diseases and cancer. It is known that zinc or iron deficiency, resulting from exposure of culture cells to membrane-permeable Zn2+ or Fe(2+)-chelators, can induced apoptosis in virally transformed cells while normal cells remain unaffected under these conditions. Apoptosis is possibly due to simultaneous inactivation of vZFP, cZFP, and/or iron containing proteins, which are essential for maintenance of cellular and viral structure and which are activated in virally transformed cells. New insights concerning apoptosis, viral metalloproteins, and novel antiviral agents will also be reviewed. From the evidence reviewed, one can infer that development of a variety of drugs that control or neutralize vZFP may lead to a new therapeutic approach directed at controlling and preventing a wide spectrum of viral diseases and cancer. Furthermore, the results suggest that these agents may be useful to prevent transmission of viral diseases. Finally, this review not only points out the limits of our understanding of this system, but also directs scientists to opportunities for future research.
Fernandez-Pol
J A
JA
Laboratory of Molecular Oncology, DVA Medical Center, St. Louis, MO 63106, USA.
Hamilton
P D
PD
Klos
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D006801:Humans; D007501:Iron; D008667:Metalloproteins / Q000187:drug effects; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000517:prevention & control; D010848:Picolinic Acids; D014777:Virus Diseases / Q000188:drug therapy* / Q000517:prevention & control; D016335:Zinc Fingers
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D008667:Metalloproteins; D010848:Picolinic Acids; D007501:Iron; C030614:picolinic acid