Why omicron makes less sick – coronavirus variant is less able to suppress the interferon response of the cells – scinexx.de

Good news in a double pack: laboratory tests confirm that the omicron variant of the coronavirus is less able to suppress the immune response of our cells. This could explain why this virus variant causes fewer illnesses than its predecessors. Also positive: the drugs developed to date against Covid-19 are still effective against omicrons, as the research team reports. This is because the virus has hardly changed at the points where these active ingredients are applied, despite the many mutations.

The omicron variant of the SARS-CoV-2 coronavirus is spreading at breakneck speed and has now become the dominant form in this country too. It differs from the wild type by around 50 mutations, including some that make it more infectious and some that allow it to evade our immune response. The antibodies formed as a result of vaccination or previous infection are less effective as a result, and the immune protection provided by T cells is largely retained.

Overall, the omicron variant is therefore more contagious and causes more infections, even in vaccinated people. On the other hand, the mutated form of the corona virus seems to cause less severe courses than its predecessor, even in unvaccinated people.

Less effective against interferon

Denisa Bojkova from the Goethe University in Frankfurt and her colleagues have now investigated why this is so. To do this, they infected hamster cells and two human cell lines with viruses of the omicron and delta variants. The cell lines differed in how intact the cells’ interferon response was. During this non-specific defense reaction, the cells produce the messenger substance interferon, which has an antiviral effect and at the same time acts as an alarm messenger substance for the immune system.

The tests showed that the omicron variant was only able to proliferate in cell lines in which the interferon response was impaired. However, if the cells had an intact and strong interferon defense reaction, the infection rate was significantly lower than that of the Delta variant. While this largely blocked the interferon response of the infected cells, the omicron variant failed to do so.

Explanation for milder gradients

“These data indicate that the omicron viruses are less able to suppress the cellular interferon response than Delta,” Bojkova and her colleagues report. In addition, the omicron variant has mutated several protein sites that normally contribute to blocking the interferon reaction.

According to the researchers, this could explain why Omikron shows less severe Covid 19 courses: “Our cell culture experiments provide an initial explanation for why Omikron infections often result in mild clinical courses: Apparently, in contrast to Delta, Omikron cannot prevent that the affected cells produce and secrete interferon,” explains co-author Martin Michaelis from the University of Kent.

Remdesivir, Paxlovid and Co also work against omicron

A second experiment by Bojkova and her colleagues provides further good news. In this they tested how well eight antiviral drugs currently being tested in clinical studies or already approved work against the omicron variant. Remdesivir, the molnupiravir derivative EIDD-1931, ribavirin, favipravir, the Paxlovid component PF-07321332 and the protease inhibitors nafamostat, camostat and aprotinin were tested.

The result here: All eight substances showed comparable effectiveness in the cell culture tests against the omicron and delta variants. “This shows that the mutations in the omicron variant have not caused any substantial changes in the drug sensitivity profile of the virus,” the scientists explain. This confirms that the viral enzymes and replication processes required for virus replication have hardly changed at Omikron.

“Although our cell culture experiments cannot of course be directly transferred to the much more complex situation in patients, they give hope that the enormous efforts to develop Covid-19 drugs were not in vain,” says Bojkova’s colleague Jindrich Cinatl. “So we can be confident that a wide range of active ingredients with different mechanisms of action will soon be available against the new omicron virus variant.” (Cell Research, doi: 10.1038/s41422-022-00619-9)

Source: Goethe University Frankfurt am Main


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