“Among the countless infectious agents of bacteria, prions, parasites, protozoa, fungi, ectoparasites and viruses, viruses are probably the greatest pandemic danger in modern times.” With the sentence begins a technical article that was published in June 2019. The two authors, Amesh Adalja and Thomas Inglesby, cite several reasons why this is so: In addition to the multiplication rate and the contagion potential of the viruses, another decisive factor is that antiviral drugs with a broad spectrum of activity are missing.
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While people today can use antibiotics to fight plague and cholera – both caused by bacteria – there is no such effective weapon against the novel corona virus. Not all bacteria can be defeated with broad-spectrum antibiotics, but why is it so difficult in comparison to develop drugs against viruses?
Viruses offer few direct targets
Above all, it is a fundamental property of viruses that significantly complicates drug development: the pathogens harness the machinery of their host’s cells for themselves. Therefore, they themselves offer few points of attack for medicines. And it is more difficult to find active ingredients that harm the viruses but not the cells – in other words: the risk of side effects is greater.
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This also illustrates the discussion about the statements of US President Donald Trump, who had encouraged scientists to examine whether it made sense to inject people with disinfectants. Irradiation (“bringing the light directly into the body”) could also be a possible remedy for the coronavirus. Both would work against the viruses, but the effects would be fatal to the person who is to be cured.
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Scientists who are researching anti-viral medication must therefore closely monitor the possible side effects of the so-called antivirals. Unfortunately, apparently simple ideas like the one with the disinfectant are not a solution.
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What helps against a virus does not help against everyone
Another challenge in the development of a broadband virostat, according to Adalja and Inglesby, are the many differences between viruses. Among other things, the genome of some pathogens consists of DNA, others of RNA, some multiply in the cell nucleus, others in the so-called cytoplasm of the cell, and the proteins that the viruses produce and need for penetration into cells or for reproduction are very different .
Despite the difficult signs, some antiviral drugs have come onto the market in recent decades, for example against HIV or against hepatitis C.
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“There are basically two ways to attack,” says virologist Heinz Feldmann, who at the US National Institute of Allergy and Infectious Diseases is researching, among other things, the development of antiviral drugs.
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First, you can Tackle virus directly, thus preventing it from entering the cell or multiplying.
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Second, you can Reduce the body’s overreaction to the viral infection.
The advantage of the second method: Because it is not directed directly against the virus, it can help with various viral infections.
An animal model for difficult courses is currently missing
Feldmann mentions another hurdle that currently exists in the development of drugs against Sars-CoV-2: “We have the problem that a good animal model for the severe Covid-19 diseases is missing.” Drug development usually begins in cell culture. Animal experiments followed. “Only then will studies begin in which the drug is used in humans.” Establishing an animal model would probably take too long in the current situation, says Feldmann.
In order to find an effective agent as quickly as possible, use active ingredients that have shown an effect on virus replication in cell cultures and that have already been tested or even approved in human studies for other treatments.
So far, however, the results have been mixed. Among other things, an investigation showed that the malaria drug hydroxychloroquine could do more harm than good. The first reports of success with the experimental Ebola drug Remdesivir were followed by disillusionment.
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Virologist Feldmann is nevertheless optimistic: “I am confident that we will find drugs that can alleviate the difficult course and prevent deaths.” He also suspects that combination therapies will come. “Many antiviral drugs have a very specific effect,” says Feldmann, “and their combination may be more effective than the administration of the individual active ingredients.”
In the search for broadband antivirals, this will probably only be a small step. But in the current situation, a drug that only works against Sars-CoV-2 would also be completely sufficient.
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