Proteases, protein cleaving agents

Protease inhibitors constitute a new class of agent for HIV infection. In its process of replication, HIV produces protein and also a protease which cleaves the protein into component parts that are subsequently reassembled into virus particles protease inhibitors disrupt this essential process. 

Proteases also are involved in viral maturation. For example, in picomavirus replication the virus RNA is translated into large virus precursor polypeptides. These then are cleaved by a viral protease(s) into the viral proteins (26,27). This opens the possibility that specific inhibitors for the viral processing protease could be used as antiviral agents. 

A novel approach to inhibition of serine proteases (or another class of proteases) involves the release of a relatively nondiscriminating agent only in the vicinity of the protease (45). Plasmin will cleave D-Val-Leu-Lys-NH-C6H4-N (CH2CH2C1) 2 releasing a powerful alkylating agent, phenylenediamine mustard. This would alkylate almost any nucleophile in the vicinity. The nucleophile could be either part of the protease or part of an adjacent protein. 

Indinavir sulfate is a protease inhibitor that inhibits human immunodeficiency virus (HIV) protease, the enzyme that cleaves viral polyprotein precursors into functional proteins in HIV-infected cells. Inhibition of this enzyme by indinavir results in formation of immature noninfectious viral particles. It is indicated in the treatment of HIV infection in combination with other antiretroviral agents. 

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