/ Geza Farkas, stock.adobe.com
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Nashville / Tennessee – The current pandemic has not yet reached its peak, according to US researchers Science Translational Medicine (2020; doi: 10.1126 / scitranslmed.abb5883) already have a promising active ingredient for the next coronavirus. The orally available EIDD-2801 protected mice from infection with SARS-CoV or MERS-CoV and cured a disease with early therapy. It was also effective against SARS-CoV-2 in cell cultures.
The effective active substances against the HI virus and the hepatitis C virus show that it is possible to fight viral infections in a targeted manner. There may also be successful treatments against MERS, SARS and COVID-19. Hopes currently rest on remdesivir, which intervenes specifically in replication. Remdesivir, or more precisely its active form GS-441524, interacts with the RNA-dependent RNA polymerase, which the RNA viruses need to multiply their genetic material.
Beta-D-N4-hydroxy-cytidine (NHC, EIDD-1931) has a comparable but probably not identical mechanism of action. EIDD-1931 is built into the RNA as a building block during the copying process. However, as with Remdesivir, this does not lead to an early termination of the RNA chain. Rather, errors occur during further copying processes, the number of which increases rapidly and soon prevents the construction of functional corona viruses.
EIDD-1931 was developed at the Emory Institute for Drug Development (EIDD) in Atlanta before the current SARS-CoV-2 pandemic began. It will likely be used as a prodrug EIDD-2801, which is available orally.
The incentive for the development of EIDD-2801 was the realization that there would be a high probability of further pandemics caused by coronaviruses in the coming years or decades. Because bats have a number of corona viruses that have the potential to infect mammals, which include more than just humans. The “swine acute diarrhea syndrome” (SADS), which is also triggered by a corona virus, killed 25,000 piglets in China in 2016.
It is only a short step to a zoonosis that spreads to humans, which is why it made sense to look for possible antidotes before COVID-19. A team led by Mark Denison from Vanderbilt University Medical Center already confirmed in November that EIDD-1931 or better his prodrug EIDD-2801 is a promising candidate for the defense against coronaviruses Journal of Virology (2019; 93: e01348-19) show in laboratory experiments. EIDD-1931 blocked the replication of several known corona viruses there. EIDD-1931 remained active even when the viruses developed resistance to remdesivir.
In the meantime, researchers have studied EIDD-1931 on mice infected with SARS-CoV and MERS-CoV. The animals were treated both before infection and after the onset of symptoms. The best effect was achieved with prophylactic administration. The treatment prevented the mice from losing weight and bleeding into the lungs.
EIDD-1931 was also therapeutically effective. However, the remedy had to be given relatively early within the first 24 hours. However, the disease develops faster in mice than in humans, so that EIDD-1931 could be effective longer. A rapid development of resistance is not to be expected due to the mechanism of action, the researchers hope.
They also examined EIDD-1931 on SARS-CoV-2. Experience has so far been limited to in vitro experiments. Nevertheless, the early start of a clinical trial is planned. However, results should only be expected in a few months. The drug could therefore be too late for the current pandemic. However, Denison is relatively certain that SARS-CoV-2 is not the last coronavirus to trigger an epidemic. © rme / aerzteblatt.de
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