19 – In search of effective medicines

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Protection against infection with the coronavirus is the most effective means of curbing its spread and the formation of new virus variants. This is where vaccine development is making rapid progress. But what helps to prevent severe courses of Covid-19? Many patients are still being treated in hospitals, and numerous people die of or with a corona infection every day. There is currently no single drug against Covid-19. However, doctors are not powerless. An overview.

What must a drug against Covid-19 be able to do?

Covid-19 runs in several stages – which determine whether and when an active ingredient is useful or even harmful. An example: At the beginning of the infection, the virus multiplies in the body’s cells. The body’s immune system becomes active and fights the infection. Medicines that support the immune system in its work or act against the virus or its reproduction are useful here. If the infection is severe and the patient has to go to the hospital and is faced with an excessive immune reaction, it would be harmful to give a drug that additionally heats up the immune system. In addition, the administration of medication is always associated with side effects.

What approaches are there for drug development?

The development of new drugs is – similar to vaccines – a complex and usually time-consuming process. In addition, there are projects to use drugs that have already been approved for other diseases for the treatment of Covid-19. The focus is on preparations from one of the following groups:

– Antiviral drugs
– anti-inflammatory drugs
– cardiovascular drugs
– antibodies; Convalescent plasma

Antiviral drugs

They should act directly against the multiplication of the viruses. Because viruses cannot divide like bacteria or other cells do: They penetrate cells and force them to switch their activity to the production of new viruses. There are two broad strategies to counteract this: one inhibits functional molecules that the virus needs to hijack the cell. Or you inhibit essential parts of the cellular production machinery that has been reprogrammed to produce viruses.

In Germany, Remdesivir is the only antiviral preparation approved for the treatment of Covid-19, but only in selected cases and if possible for an early stage of the disease. Study data show a 33 percent reduction in the duration of the illness, but only in severe cases. A benefit of remdesivir has not been proven for a mild to moderate course.

A benefit for the treatment of Covid-19 with preparations such as lopinavir and ritonavir has been discussed but not proven. Both are used in the treatment of HIV infection and act on enzymes that the virus needs to make functional molecules.

In Latin America in particular, ivermectin was often used to treat certain worm parasites in veterinary medicine. A laboratory study initially fueled the hope that the antiviral effect against Sars-CoV-2 observed here could also be demonstrated in humans. A work published in the specialist portal JAMA, however, based on a randomized patient study, comes to the conclusion that – at least in the case of a mild course of the disease – there is no clear effect.

Anti-inflammatory drugs

One problem with severe Covid-19 courses is an excessive reaction of the immune system. In other words, it is no longer the virus that is causing the main problems, but the body’s response. This is where steroids like dexamethasone come into play. Dexamethasone belongs to the group of cortisones, which slow down the immune system. Preliminary patient data from the UK show that administration of dexamethasone in severe cases reduces mortality from Covid-19. In Germany, too, dexamethasone is used in severe cases – that is, when the patient is given additional oxygen.

Research is also being carried out into the use of monoclonal antibodies in anti-inflammatory therapeutic approaches. The principle: to specifically inhibit a switching point of the excessive immune reaction. To do this, the antibodies are constructed in such a way that they are directed against structures of the immune system. The focus here is on the drugs tocilizumab and anakinra, which are normally used against autoimmune diseases. There are several studies on the treatment of seriously ill Covid-19 patients with tocilizumab, none of which has yet gone through the peer-reviewed control procedure. Some, including the most extensive from the UK, suggest that concomitant treatment with tocilizumab and dexamethasone may reduce mortality in critically ill Covid-19 patients. The Robert Koch Institute has classified tocilizumab as a drug with a proven benefit in the treatment of Covid-19. Such a benefit has not yet been demonstrated for anakinra. Both preparations are currently not approved for the treatment of Covid-19 in Germany.

Cardiovascular drugs

The main concern here is the use of preparations that have already been approved. In the course of the pandemic, it became clear that the formation of thromboses, i.e. blood clots, is a common complication of Covid-19 patients who have to be treated in hospital. The risk of this is apparently increased especially in the seriously ill. The Robert Koch Institute recommends using such anticoagulants prophylactically at an early stage.

antibody

The antiviral drugs include the antibody preparations REGN-CoV-2 from Regeneron and Bamlanivimab from Eli Lilly, which are not yet approved in Germany. The federal government has bought both funds for the treatment of high-risk patients. REGN-CoV-2 consists of a combination of two monoclonal antibodies, Bamlanivimab contains one type of monoclonal antibody. Both act like a passive vaccination and are intended to prevent Sars-CoV-2 from entering human cells. They work by binding to characteristic structures on the surface of Sars-CoV-2, more precisely to the spike protein with which it binds to receptors on the surface of human cells. The preparations are particularly useful in the early phase of the infection, when the virus is multiplying rapidly. Here you can read more about the functionality, advantages and disadvantages of antibody drugs.

Antibodies are also contained in convalescent plasma – i.e. in the blood plasma of recovered Covid 19 patients. Their effect depends on the severity of the illness and how long ago it was. In contrast to the monoclonal antibodies from the laboratory, this is a mixture of antibodies against various virus structures that the body has formed itself in the course of an infection with Sars-CoV-2. Such a purified serum can be administered at an early stage of the disease to protect against a severe course. This method has also been used in other virus outbreaks, such as the 2014 Ebola epidemic in West Africa. Convalescent plasma has not yet been approved for the treatment of Covid-19 in Germany. The Robert Koch Institute considers deployment in individual, severe cases to be conceivable.

Research approaches: a nasal spray as virus prophylaxis?

Research is also being carried out into drugs that are supposed to prevent viruses from implanting in the mucous membrane, for example after contact with an infected person. To this end, an international scientific team is working on a nasal spray that is supposed to prevent the virus from entering the cells of the nasal mucous membrane. This worked in animal experiments with ferrets, as the researchers write in the journal Science. The animals that had previously been treated with the spray did not become ill after prolonged contact with infected conspecifics. The virologist Sandra Ciesek speaks in the NDR of an important research approach, but emphasizes that the road to a possible prophylactic drug of this type is “a long one” that will “probably take years”.

Molnupiravir is an example of research into new antiviral drugs: initially developed for the treatment of flu, but failed before approval. The manufacturer, the US pharmaceutical company Merck & Co, is now reporting initial successes from tests with ferrets: 24 hours after the start of the antiviral treatment, no more infectious particles were detectable in the smears. Studies in mice produced similar results. Molnupiravir is currently in clinical trials for use in humans.

Another example of the development of new antiviral drugs is provided by the German company Formycon. She is developing a preparation whose active ingredient molecule is modeled on the cell receptor used by the virus. The company argues that this means that the preparation can also be expected to have a good effect against virus variants. One problem for this type of active ingredient is to maintain the original function of the cell receptor in the organism. Formicon tries to solve this by equipping its active ingredient molecule with another functional unit. The preparation is at the beginning of the so-called preclinical development, i.e. before the clinical studies, the success of which is necessary for approval. According to its own information, the company is aiming for emergency approval in the coming year.

The Milken Institute – an American think tank that collects research results on Covid-19, among other things – maintains a list of the preparations that are being examined as vaccines or therapeutic agents in the pandemic.
Our research team has put together details on research into other drugs. The guideline on the inpatient treatment of COVID-19 patients, which was compiled by several specialist societies, is aimed primarily at professionals.

(Stand: 8.3.21)

Further articles on the coronavirus

We have created a news blog. In view of the large amount of information, this provides an overview of the most important current developments.

+ Covid-19: Current figures on the coronavirus in Germany (as of March 30)
+ Holidays: What will happen to the Easter holiday? (As of March 23)

Test and protection

+ Protection: The vaccination ordinance: who will be vaccinated first, who will be vaccinated later? (As of March 4th)
+ Vaccination appointment: how can I get vaccinated when and where? (As of March 4th)
+ Vaccines: When children could also be vaccinated (as of March 26)
+ Vaccinations: What is known about the side effects of vaccines (as of March 19)
+ Sick people: New findings in the search for drugs (as of March 8th)
Treatment: How does an antibody drug work and when does it make sense? (As of February 26th)

Contagion and Transmission

+ Virus variants: how dangerous are the new mutations of the coronavirus? (Status: 13.03.)
+ Opponents of infection protection measures: What AfD and lateral thinkers have to do with the spread of the coronavirus in Germany (as of 02/09)
+ Transfer: What role aerosols play (as of January 22)
+ Excess mortality: how deadly is the coronavirus really? (Status: 13.03.)
+ Travel warning: The current list of risk areas (as of March 27)

You can also find the Dlf news on Twitter at: @DLFNews.





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