Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

The life cycle of many viruses depends upon viral proteases for the cleavage of high molecular weight precursor viral proteins in order to yield functional products or by catalyzing the processing of the structural and non-structural proteins that are necessary for assembly and morphogenesis of viral particles. A partial list of human disease-associated viruses encoding protease(s) in their genomes include flaviviruses such as: hepatitis C virus (HCV), West Nile virus (WNV), dengue fever virus (DFV) and yellow fever virus (YFV); retroviruses such as HIV-1; picornaviruses such as coxsackievirus, poliovirus and hepatitis A virus; nidoviruses such as coronaviruses (CoV), including the severe acute respiratory syndrome (SARS) causative SARS-CoV; and herpesviruses such as varicella-zoster virus (VZV) and Epstein-Bar virus (EBV) [503] [504] [505] . As expression of the viral protease distinguishes an infected cell from surrounding healthy tissue, limiting virus production and spread by a viral-protease activated toxin that specifically eradicates infected cells may comprise an attractive antiviral approach (Figure 1 ). Selected preclinical studies in the field are described in the following chapter. Information about the reviewed intracellular activated toxins is also summarized in Table 3 .