RNA viruses possess a single strand of RNA and adopt different
- RNA sense (positive) may serve directly as mRNA and be translated
into structural protein and an RNA-dependent RNA
- RNA antisense (negative) contains an RNA-dependent RNA
polymerase that transcribes the viral genome into mRNA. Alternatively,
the transcribed RNA can act as a template for further
viral (antisense) RNA.
- Retroviruses have single-stranded sense RNA that cannot act as
mRNA. This is transcribed into DNA by reverse transcriptase and
incorporated into host DNA. The subsequent transcription to
make mRNA and viral genomic RNA is under the control of host
Viral nucleic acid is covered by a protein coat of repeating units
(capsids), with either icosahedral (spherical) or helical (arranged
around a rotational axis) symmetry.
Repeating units reduce the number of genes devoted to production
of the viral coat and simplify the process of viral assembly.
A lipid envelope derived from host cell or nuclear membrane surrounds
some viruses. The host membrane may incorporate viralencoded
antigens that may act as receptors for other host cells.
Enveloped viruses are sensitive to substances that dissolve the lipid
membrane (e.g. ether).
The intracellular location of viruses and their use of host cell
systems pose a challenge to the development of antiviral therapy.
Drugs may work at different stages of viral replication.
Amantadine/rimantidine prevents uncoating and release of influenza
RNA but resistance arises readily. Pleconaril inhibits uncoating
of picornaviruses and is active against enteroviruses and
rhinoviruses; it is absorbed orally and clinical trials suggest it
shortens clinical symptoms.
Aciclovir is selectively converted into acyclo-guanosine monophosphate
(acyclo-GMP) by viral enzymes, then into a potent
inhibitor of viral DNA polymerase by host enzymes. The acyclo-
GMP causes viral DNA chain termination. Resistance occurs
through the development of deficient thymidine kinase production
or alteration in the viral polymerase gene. The drug can be taken
orally and crosses the blood-brain barrier. Other agents (e.g. ganciclovir)
work in a similar way.
Reverse transcriptase inhibition
Lamivudine inhibits the reverse transcriptase of hepatitis B and
HIV (see below). Nucleoside and nucleotide inhibitors are being
developed as alternative treatments for hepatitis B; these include
adefovir, entecavir, tenofovir, telbivudine and clevudine.
Ribavirin is a guanosine analogue that inhibits several steps in
viral replication including capping and elongation of viral mRNA.
It is active against respiratory syncytial virus, influenza A and B,
parainfluenza virus, Lassa fever, hantavirus and other
Nucleoside reverse transcriptase inhibitors
Nucleoside reverse transcriptase inhibitors (NRTIs) inhibit reverse
transcriptase by being incorporated as faulty nucleotides. Examples
include the longest established antiretroviral drug zidovudine
(AZT), plus lamivudine (3TC), stavudine (d4T), tenofovir, didanosine
(ddI) zalcitabine (ddC) and abacavir (see HIV infection and AIDS
Non-nucleoside reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit
reverse transcriptase directly; examples include nevirapine, efavirenz,
delavirdine and etravirine. They have been shown to be
effective agents in combination regimens. As resistance occurs
after a single mutation, they are used in maximally suppressive
Protease inhibitors target the HIV-encoded protease. They are
highly effective antiretroviral compounds that cause significant
falls in viral load. They include atazanavir, indinavir, lopinavir,
ritonavir and saquinavir. Ruprintrivir acts in the same way against
human rhinovirus 3C protease. It is administered by nasal spray
and appears to have useful activity in rhinovirus infection.
Enfuvirtide inhibits binding with gp134; maraviroc inhibits binding
to CCR5 preventing fusion. Both agents are used for salvage
therapy in AIDS (see HIV infection and AIDS
Neuraminidase inhibitors including zanamivir and oseltamivir
inhibit the final stage in the release of virus from the host cell.
These agents are being developed to block the insertion of the HIV
viral genome into the DNA of the host cell.
Infections with hepatitis B and hepatitis C can also be treated with
α-interferon, a host cytokine.