Ribavirin

Hardly anyone doubts that hepatitis C (170 million infected people worldwide) and HIV (40 million infected people) are global problems. Both viral infections have in common that no complete cure, but only a mitigation or suppression of the course of the disease is possible. Among other things, the virus-inhibiting agent plays a role here Ribavirin an important role.

What is ribavirin?

Ribavirin is an antiviral. As such, it is one of the few active ingredients that can even be used 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®).

From a chemical point of view, it is the sugar ribose, to which a triazole-carboxamide molecule is bound. The decisive factor here is that ribavirin thus becomes a so-called nucleoside analog: It has a structure similar to guanosine, a building block (nucleoside) that occurs in RNA and DNA.

RNA is very similar to the genetic material DNA and, among other things, plays a decisive role in human metabolism; some viruses even have RNA as genetic material.

Pharmacological effect

Ribavirin After ingestion, it is first converted into ribavirin phosphate in the liver. The resulting metabolic product has a virustatic effect in at least two ways.

On the one hand, the molecule binds to the enzyme IMP (inosine monophosphate dehydrogenase), which is indirectly responsible for the production of guanosine triphosphate (GTP) in the cells. GTP is a component of every virus genome. If there is too little of it, the virus cannot multiply its genetic material; no new viruses can emerge.

On the other hand, due to its nucleoside-like structure, ribavirin phosphate is, so to speak, incorrectly incorporated into the RNA or DNA of viruses. The genetic material is replicated by enzymes called polymerases, which run along the single strands of DNA / RNA and attach the appropriate complementary building blocks.

If a polymerase hits the wrong building block, the sensitive interplay between enzyme and genome is so disturbed that it stops its activity and "falls off". You can compare this to a small coin derailing a train. Other mechanisms of action are also discussed in research.

Medical application & use

Ribavirin In addition to the areas of application already mentioned, it is also used for RSV (respiratory syncytial virus), influenza and herpes viruses. However, retroviruses are not recorded.

The Robert Koch Institute now advises against using it for RSV, as no clear effectiveness could be determined. In some tropical viral infections such as Lassa fever or Crimean-Congo fever, ribavirin could be the only effective drug, although study data suggest an effect only in the early stages of the disease.

The intake takes place against the RSV in the form of a spray, for hepatitis C and the other viral diseases the drug is given as capsules. Eating a high-fat meal at the same time appears to improve absorption in the intestinal tract.

Pregnant women should not take ribavirin at all. Couples wishing to have children are advised to wait 6 months after completing therapy. The reason is the possible reproductive harm of the agent (see below).

Risks & side effects

Probably the worst side effect of Ribavirin is hemolytic anemia, a form of anemia in which the red blood cells (erythrocytes) are destroyed.

The chemically modified metabolic product of ribavirin accumulates especially 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) in such a way that they are destroyed or commit programmed "suicide".

A second possible side effect, but so far only proven in animal experiments, is damage to fertility. The 6 months of latency listed above are due to the fact that ribavirin is only completely eliminated from the body after this period. Since erythrocytes accumulate the substance (see above), one has to wait a whole life span for this cell type.

Ribavirin should not be taken together with zidovudine and didanosine, as they can cause severe side effects such as oxygen starvation due to acute anemia and liver damage due to mitochondrial toxicity.