Virus-specific enzymes

The complete complex of nucleic acid and protein, packaged in the virus particle, is called the virus nucleocapsid. Although the virus structure just described is frequently the total structure of a virus particle, a number of animal viruses (and a few bacterial viruses) have more complex structures. These viruses are enveloped viruses, in which the nucleocapsid is enclosed in a membrane. Virus membranes are generally lipid bilayer membranes, but associated with these membranes are often virus-specific proteins. Inside the virion are often one or more virus-specific enzymes. Such enzymes usually play roles during the infection and replication process. 

Early steps in replication of the virus nucleic acid, in which the host cell biosynthetic machinery is altered as a prelude to virus nucleic acid synthesis. Virus-specific enzymes may be made ... 

As we have noted, the outcome of a virus infection is the synthesis of viral nucleic acid and viral protein coats. In effect, the virus takes over the biosynthetic machinery of the host and uses it for its own synthesis. A few enzymes needed for virus replication may be present in the virus particle and may be introduced into the cell during the infection process, but the host supplies everything else energy-generating system, ribosomes, amino-acid activating enzymes, transfer RNA (with a few exceptions), and all soluble factors. The virus genome codes for all new proteins. Such proteins would include the coat protein subunits (of which there are generally more than one kind) plus any new virus-specific enzymes. 

It has been found that viruses (Appendix 10) utilize a number of virus specific enzymes during replication. These enzymes and the processes they control are significantly different from those of the host cell to make a useful target for medicinal chemists. Consequently, antiviral drugs usually act by either inhibiting viral nucleic acid synthesis, inhibit attachment to and penetration of the host cell or inhibit viral protein synthesis. 

Proteins never serve as templates for RNA. However, RNA chains can in rare circumstances reverse the flow of information from RNA to DNA. An example of this is the infecting RNA of retroviruses that serves as a template for the synthesis of a single-stranded complementary DNA (cDNA) chain that functions as a template for a complementary DNA chain. The resulting double-stranded DNA then acts as a template for the synthesis of the original viral RNA chain. The virus-specific enzyme, reverse transcriptase, catalyzes the synthesis of DNA on the RNA template. Little if any reverse transcriptase activity is present in normal cells, so that very little DNA is formed on RNA templates. 

The uncoating process has been shown to be carried out by virus-specific enzymes, synthesized at the direction of viral mRNA. The mRNA in turn has used a portion of the viral DNA as the template. Experimentally, at least, protein synthesis inhibitors can inhibit the production of these uncoating enzymes. However, due to a lack of significant specificity, the compounds were of no clinical value. The antimalarial drug chloroquine is the only agent of any consequence found to have any inhibiting effect on the uncoating of a virus, namely, Newcastle disease virus. 

Mechanisms Ganciclovir, a guanine derivative, is triphosphorylated to form a nucleotide that inhibits DNA polymerases of CMV and HSV but does not cause chain termination. The first phosphorylation step is catalyzed by virus-specific enzymes in both CMV-infected and HSV-infected cells. CMV resistance mechanisms include changes in DNA polymerase and mutations in the gene that codes for the activating viral phosphotransferase. Thymidine kinase-deficient HSV strains are resistant to ganciclovir. 

Recently, it has been shown that some virus-infected cells induce virus-specific enzymes such as thymidine kinase or DNA polymerase. These virus-induced enzymes have been proven to differ from their cellular enzymes in terms of such properties as substrate specificity. 

The viruses are cell parasites they use the cell machinery for replication. Targeting the virus-specific enzymes is an attractive option, and may lead to significant improvement for the treatment of specific viruses. Since obtaining accurate viral diagnosis is difficult and time-consuming, the start of a specific... 

King, D.P. et al., The use of monoclonal antibodies specific for seal immunoglobulins in an enzyme-linked immunosorbent assay to detect canine distemper virus-specific immunoglobulin in seal plasma samples, J. Immuno. Methods, 160, 163, 1993. 

Reverse transcriptase is a retroviral-specific enzyme and is essential to the virus. Drugs that inhibit this enzyme are... 

Replication of the human immunodeficiency virus (mV), the causative agent of AIDS, is susceptible to targeted interventions, because several virus-specific metabolic steps occur in infected cells (A). Viral RNA must first be transcribed into DNA, a step catalyzed by viral reverse transcriptase." Double-stranded DNA is incorporated into the host genome with the help of viral inte-grase. Under control by viral DNA, viral replication can then be initiated, with synthesis of viral RNA and proteins (including enzymes such as reverse transcriptase and integrase, and structural proteins such as the matrix protein lining the inside of the viral envelope). 

Gottschalk A. Neuraminidase the specific enzyme of influenza virus and vibrio cholerae. Biochem Biophys Acta 1957 23 645-646. 

Mechanism of Action. Oseltamivir and zanamivir inhibit a specific enzyme (neuraminidase) that the influenza virus uses to complete its biosynthesis and release. By inhibiting this enzyme, these drugs impair a key step in viral replication, and reduce the ability of the virus to infect other respiratory cells. 

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