Hardly anyone doubts that hepatitis C (170 million infected worldwide) and HIV (40 million infected) are global problems. Both viral infections have in common that no complete cure is possible, but only a mitigation or suppression of the course of the disease. Here, among other things, the virus-inhibiting agent ribavirin plays an important role.
What is ribavirin?
Ribavirin is a viral inhibitor. As such, it is one of the few agents that can be used at all in therapy against viruses. Ribavirin is a virustatic agent. As such, it is one of the few active substances that can be used at all in therapy against viruses. It has been available in Germany since 1993 under the trade name Virazole (Switzerland/Austria: Copegus, Rebetol). For hepatitis C therapy, it is administered in combination with interferon alpha-2b (intron A). Chemically, it is the sugar ribose to which a triazole carboxamide molecule is bound. Crucially, this makes ribavirin what is known as a nucleoside analog: It has a similar structure to guanosine, a building block (nucleoside) found in RNA and DNA. RNA is very similar to the genetic material DNA and plays a crucial role in human metabolism, among other things; some viruses even possess RNA as genetic material.
Pharmacological action
Ribavirin is first converted to ribavirin phosphate in the liver after ingestion. The resulting metabolite has a virustatic effect in at least two ways. First, the molecule binds to the enzyme IMP (inosine monophosphate dehydrogenase), which is indirectly responsible for the production of guanosine triphosphate (GTP) in cells. GTP is a building block of every viral genome. If too little of it is present, the virus cannot replicate its genetic material; no new viruses can be produced. Second, because of its nucleoside-like structure, ribavirin phosphate is incorporated into the RNA or DNA of viruses by mistake, so to speak. The duplication of the genetic material is carried out by enzymes called polymerases, which run along the DNA/RNA single strands and attach the matching complementary building blocks in each case. If a polymerase comes into contact with the wrong building block, the sensitive interplay between the enzyme and the strand of genetic material is disturbed in such a way that it ceases its activity and “falls off”. This can be compared to a small coin derailing a train. Other mechanisms of action are also being discussed in research.
Medical application and use
Ribavirin is also used for RSV (respiratory syncytial virus), influenza, and herpes viruses, in addition to the applications already mentioned. Retroviruses, however, are not covered. The Robert Koch Institute now advises against use for RSV, as no clear efficacy has been established. In some tropical viral infections such as Lassa fever or Crimean-Congo fever, ribavirin may be the only effective drug, although study data suggest an effect only in early stages of the diseases. For RSV, the drug is taken in the form of a spray; for hepatitis C and the other viral diseases, the drug is administered as capsules. Simultaneous consumption of a high-fat meal appears to improve absorption in the intestinal tract. Pregnant women should not take ribavirin at all. Couples of childbearing potential are advised to wait 6 months after completing therapy. This is because of the potentially reproductive-damaging effects of the drug (see below).
Risks and side effects
Probably the worst side effect of ribavirin is hemolytic anemia, a form of anemia in which the red blood cells (RBCs) are destroyed. The chemically modified metabolite of ribavirin accumulates particularly in the erythrocytes because they lack the enzymatic equipment to remove the molecules. If ribavirin phosphate is not eliminated, it weakens the cells in their fight against harmful molecules (e.g. free radicals) to such an extent that they are destroyed or commit programmed “suicide”. A second possible side effect, but so far only proven in animal studies, is damage to reproductive ability. The 6-month latency mentioned above is due to the fact that ribavirin is only completely excreted from the body after this time. Since erythrocytes accumulate the substance (see above), a whole lifespan of this cell type must be waited for.Ribavirin should not be taken with zidovudine and didanosine, as this may cause severe side effects such as oxygen deprivation due to acute anemia and liver damage due to mitochondrial toxicity.