Until recently, medicine hasn't had any way to treat virus
es once their infection has taken hold in the body. Unlike bacteria
, which we've been able to treat with antibiotic
s for almost a hundred years, there are no general strategies for fighting viral infection
s. Instead, we have to make a separate immunization
for each strain of each virus, and
determine if it is safe and effective. Vaccinations are preventative only (there are exceptions, e.g. the rabies vaccine
), and generally take a few days to make the body's immune system
effective against whatever virus they target. With developments in genomics
since the mid-1980's, we're finally getting to a point where a virus's behavior can be analysed in enough depth to specifically shut down its action in vivo
Viruses are so difficult to treat because of the way they work. Where bacteria are self-contained, living organisms, viruses must infect a host cell and high-jack its life processes to reproduce. They have virtually no active mechanisms of their own -- zero metabolism besides the couple of steps used to invade the host cell -- so they can't be attacked directly the way antibiotics attack bacteria. Immunization works by exposing the immune system to a dummy virus (or viral fragment, or single protein, etc.) that isn't dangerous by itself. The immune system makes antibodies for the dummy which, if the immunization is effective, are also antibodies for the real, dangerous virus.
Instead of dealing with the immune system at all, modern antiviral medications are taken into host cells, and change their working in such a way that an attacking virus can't use them. This is where problems arise. Processes within cells are there to keep the cell functioning properly, so disrupting those processes can be dangerous to the cell. Heavy research must be done on each antiviral medicine to make sure it doesn't do fatal damage to cells, which would be almost as undesirable as letting the virus proliferate. So far, this research has uncovered four avenues of intracellular disruption that fit the bill:
- Keep viruses out of the cell. To enter the host cell, the virus must fuse to a receptor channel somewhere on it -- viruses can't break through cell walls, they have to be "let in." Viruses also have a protein coat surrounding their RNA which must be dissolved as part of the viral entry procedure. If the coat isn't dissolved, the host cell can't process the RNA or DNA and make it into more viruses. Stopping entry can be done by blocking either the channel used by the virus or the host cell protein which uncoats the viral genome. Research is being done into blocking the CCR5 proteins on helper T cells so they cannot take up the HIV virus, and a soon-to-be-approved anti-cold drug named pleconaril works by inhibiting uncoating.
- Screw up transcription. After the viral RNA or DNA has been released inside the cell, it has to be transcribed once or more before protein production may start for new viruses. Blocking this transcription is thus a potentially effective strategy. Blocking is done with nucleotide or nucleoside analogues, which resemble the building blocks of DNA or their precursors, respectively. When the transcription process attaches one of these analogues to the strand it's working with, the strand becomes useless as any kind of template. This would be great if the analogues only targeted viral transcriptions, but they can be dangerous since they also disrupt cellular ones. AZT is a very effective and relatively non-toxic nucleoside analogue used against HIV, and Acyclovir works the same way against herpes simplex.
- Stop protein production. Producing proteins requires that transcription factors attach to viral DNA, which switch on production of messenger RNA, which is used as the protein template. With genomics, we've become aware of the targets of these factors, so we can disable mRNA production by masking those targets on the DNA. These masks are known as antisense drugs. Since these drugs specifically attach to viral DNA, they don't do much or any damage to the cell function, and are the least toxic form of antiviral medication.
HIV and a few other viruses have DNA that produces one long strand of mRNA, which can only be converted by ribosomes into one long protein chain. By itself this chain is non-functional -- it must be split up into its individual constituent proteins before viral replication is successful. This splitting is done by an enzyme named protease, which works by traveling down the protein chain looking for the specific places it's supposed to cut. During the 1990's protease inhibitors were discovered, which stop the enzyme from doing its job, and thus keep HIV etc. in check. Protease is part of the host cell's system, unfortunately, and disturbing it is known to cause side effects.
- Keep new viruses from circulating. Besides proteins that enable viruses to enter cells, viruses also have mechanisms to help them escape. Influenza, for instance, has a protein called neuraminidase that lets it escape host cells. Two new influenza drugs, oseltamivir and zanamivir, both work by disabling neuraminidase. Since these drugs target the virus rather than the host, they are (again) relatively non-toxic.