Viruses can exist and reproduce only as extreme cellular parasites because they do
not possess a complete synthetic machinery for independent survival. Accordingly,
viruses are obligate parasites, able to replicate only in living cells. To survive, a virus
must first penetrate a host cell. Viruses consist of infectious DNA or RNA (but not both)
wrapped in a protective protein coat, which shows helical or spherical symmetry and
which may show molecular appendages. The replication and assembly of such complex
structures is not a spontaneous self-assembly but is instead directed by enzymes and by
“assisting proteins” that collectively form a biosynthetic framework. The replication of
viruses is very different from that of higher organisms. In some, such as the DNA
viruses, transcription and translation occur; whereas in others, like the single-stranded
RNA viruses, the RNA is its own messenger and activates an RNA-directed DNA poly-
merase.The latter viruses are known as retrovirusesbecause of the reversal of the normal
DNA–RNA–protein sequence; the DNA produced in this reverse way then becomes the
template for viral RNA and protein. The virus then uses the enzymes, nucleotides, and
amino acids of the infected host cell to build the virion. Because of this diversion of
starting material and synthetic capacity, the infected cell may die, with virions being
released to infect other cells (lyticviruses); alternatively, the viral DNA may join the
infected cell by recombination, which then continues to produce virions (lysogenic
viruses). In some instances, the host cell is transformed into a malignant, cancerous cell
by the virus, which is obviously a process of great interest to the mechanistic under-
standing of human disease. The discovery of cancer genes (oncogenes) will ultimately
shed more light on the process of viral-induced carcinogenesis.
A high proportion of human and animal diseases are caused by viruses, from the
common cold to poliomyelitis, rabies, hepatitis, and many others. Table 9.1 provides an
overview of viruses causing diseases in humans. In the last two decades of the twentieth
century, the emergence of the AIDS epidemic focused attention on the need to develop
548 MEDICINAL CHEMISTRY
Figure 9.1 The viral infectious unit, or virion, consists of a nucleic acid encased in a protein shell.
The various structural components of the virion exhibit differing functional properties and thus
afford a variety of targets for antiviral drug design.