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COVID-19: Drug tests in progress
Experts believe that developing a vaccine against the SARS-CoV-2 coronavirus will take even longer. Therefore, efforts are being made to treat the disease COVID-19 better. To this end, not only are new medicines developed, but also existing preparations are tested. Tests with promising drugs are currently underway.
Even if the corona pandemic has been going on for months, there is still no internationally approved active ingredient against the disease COVID-19 caused by the new SARS-CoV-2 coronavirus. Austrian researchers are now testing promising COVID-19 drugs on SARS-CoV-2 samples.
Effect tested in cell culture experiments
According to a message, possible drugs are currently being tested for their effects against SARS-CoV-2 pathogens in cell culture experiments in the BSL-3 laboratory at the Medical University of Graz, the laboratory with the highest safety equipment in Austria.
In the interdisciplinary research project, the researchers set themselves the goal of building up a preclinical database of active substances. Antiviral drugs should therefore be brought to clinical use much faster. In addition, drugs for the therapy of already infected COVID-19 patients are being developed.
Faster availability with high impact
As the press release says, the development of coronavirus vaccines is advancing at an unprecedented rate worldwide. Nevertheless, it often takes years until a suitable vaccination is available.
For this reason, a research project by the Austrian Center of Industrial Biotechnology (acib), the Medical University of Graz and the Graz biotech company Innophore is also concentrating on finding, evaluating and preclinical testing of a certain class of active ingredients that combine faster availability with high effectiveness.
We are talking about antiviral drugs, such as those developed against HIV, MERS or SARS. These inhibit the activity of enzymes that viruses need to reproduce and prevent viruses from entering, for example, lung cells. This means that the agents can on the one hand prevent the infection of cells and on the other hand suppress the multiplication of viruses in infected cells. Both strategies are important pillars for the therapy of COVID-19 sufferers.
Potential drug candidates identified
Because many of these drugs are already approved on the market, they can be converted into corona drugs relatively quickly. "This repurposing has the advantage that chemical substances can be identified more quickly and can be used very quickly for COVID-19 patients due to their approval for other diseases," explains Innophore CEO and acib senior researcher Christian Gruber.
“In the first step, we focus on finding active substances against the coronavirus. Therefore, in another project, we use computer modeling and simulation to screen over two billion individual active substances against COVID-19, ”the expert continued.
In addition, in the acib cooperation project, the computer-assisted search is supplemented with high-throughput screening in the laboratory. According to the information, robotic systems on the one hand test the drugs proposed in the computer models and, on the other hand, new compounds from libraries of hundreds of thousands of chemical compounds are tested for their effects directly in the laboratory. They show in real time whether the computer models are correct and the backward flow of the real measured data into the simulations can improve the prediction accuracy of the computer models.
"We are pleased that we have already identified a number of potential drug candidates," says Gruber. These starting substances are currently being optimized in the BSL-3 high-security laboratory at the Med Uni Graz and subjected to various in vitro tests in order to clarify their suitability for later clinical studies.
Highly infectious viruses
In order to test substances for their effects, they have to be brought together in cell cultures with specially propagated, living pathogens such as the highly infectious SARS-CoV-2 Coronavirus. In order to ensure the protection of people and the environment, a laboratory infrastructure such as that available at the Med Uni Campus Graz is required.
"The BSL-3 laboratory currently has the highest available safety standard for laboratories in Austria," says Kurt Zatloukal from the Diagnostic and Research Institute for Pathology at the Medical University of Graz.
The in-vitro tests of antiviral drugs follow three phases: “This first phase of the Covid-19 experiments has already been successfully completed. We carry out cytotoxicity tests to ensure that the compounds do not cause any general damage to the cells and, in a further step, determine the concentration in which the substance can be used, ”said Zatloukal and Gruber.
To this end, they received OC-43 isolates (a subset of coronaviruses) from the Medical University of Vienna as well as the SARS-CoV-2 virus strain and virus cultures isolated from the Charité - Universitätsmedizin Berlin, which were created by a total of 17 Styrian COVID-19 patients and include different genetic variants of the virus. According to the researchers, experiments they conducted can provide information about whether a drug can prevent the virus from multiplying.
Development time is shortened
In the second, recently started process phase, the researchers test the compounds for their action against COVID-19. So-called human organoids are used to simulate the absorption and effects - as well as possible side effects - of medications in the human body as precisely as possible.
“These are cell groups grown in the laboratory, whose structure and capabilities largely resemble those of organs. This next generation of new, organic tools allows the effects of substances in cells - outside the body - to be examined very closely, ”explains Zatloukal.
“We try to gather as much information as possible about how substances can behave in the human body in such model organs in the Petri dish. This reduces the use of animal experiments and shortens the development time for SARS-CoV-2 drugs. "
Develop new drug groups
In the last phase, the scientists test whether the genetic diversity of different virus subclasses of SARS-CoV-2 influences the mode of action of medication. According to the researchers, the virus isolates of the Styrian COVID-19 patients are sequenced and subjected to in-vitro and in-silico experiments together with reference strains from other countries. This is necessary to show that a chemical substance could be suitable for wide clinical use.
“Our research work relates to the so-called pre-clinical development phase of a drug. The more extensive and convincing the data are, the greater the chance that the substances will be further developed by the industry and will ultimately be used on humans. What we want to show within the one-year acib-funded project is that our approach to identifying antiviral drugs and testing their effectiveness works, ”says Zatloukal.
According to the expert, what applies to the cooperative approach to cooperation could also apply to the use of medicines: "In the end, it may be necessary to combine several concepts to combat COVID-19." (Ad)
Author and source information
This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.