Immune defense protein inhibits SARS-CoV-2 multiplication by a factor of 20 – healing practice

SARS-CoV-2: Protein inhibits viral load by a factor of 20

Numerous research institutions around the world are busy developing agents against the SARS-CoV-2 coronavirus and the COVID-19 disease caused by the pathogen. Now there is a glimmer of hope: Experts from Germany report on a protein that inhibits the virus from multiplying by a factor of 20.

Scientists from the Würzburg Helmholtz Institute for RNA-based Infection Research (HIRI) and the Helmholtz Center for Infection Research (HZI) in Braunschweig have for the first time demonstrated how ZAP, a protein of the human immune system, is responsible for the multiplication mechanism of the coronavirus SARS-CoV-2 inhibits and can reduce the viral load by 20 times. The findings can help develop antivirals to fight the pandemic.

Immunomodulatory and antiviral protein

Like in a Message explained, SARS-CoV-2 and other viruses whose genome consists of ribonucleic acids (RNA) use a multiplying trick known as programmed ribosomal reading frame shift.

These pathogens prove to be masters of manipulation: the viruses penetrate the host cells and hijack the process that the cells use to read genetic information from a messenger RNA and to produce proteins. The pathogens change the strictly regulated reading direction and can thus produce their own proteins and multiply.

In search of ways to prevent this trick of SARS-CoV-2 from reproducing, researchers at HIRI have now identified a restriction factor called ZAP.

ZAP (from the English: Zinc Finger Antiviral Protein) is known as an immunomodulatory and antiviral protein: “ZAP is a multifunctional molecule in the immune system that can calm an excessive immune response and shut down viral activity,” explains Jun. Prof. Neva Caliskan , Research group leader at HIRI and head of the now in the specialist journal “Nature Communications“Published study.

Attractive drug target

So far, it has not been researched whether and how proteins such as ZAP intervene in the ribosomal reading frame shift of SARS-CoV-2. “The reading frame shift has become established as the heart of virus replication. And that is exactly what makes them an attractive drug target, ”says Matthias Zimmer, one of the two first authors of the study.

“Interestingly, we were able to prove that ZAP binds to the viral RNA that triggers the reading frame shift,” adds the HIRI doctoral student from Caliskan’s research group “Recoding Mechanisms in Infections”.

“ZAP intervenes in the structural folding of the coronavirus RNA and prevents the signal that SARS-CoV-2 sends out to induce the host cells to produce its replication enzymes,” explains HIRI doctoral student Anuja Kibe, second lead author of the study, the antiviral Effect of protein.

And what’s more: In collaboration with researchers at the HZI in Braunschweig, the team was able to prove that host cells with an increased ZAP level have an approximately 20-fold reduced virus quantity. Thus, the increased occurrence – or lack of – of the protein could also be an indicator of whether a corona infection is mild or severe.

However, further research is required to fully understand the underlying molecular mechanisms. But the study results are already extremely promising: “Our findings give reason to hope that ZAP could be used as a template to develop possible new antiviral agents,” says Caliskan.

As is finally explained in the communication, the so-called zinc finger antiviral protein (ZAP for short) is a multifunctional protein of the immune system and inhibits the replication of certain viruses. It comes in a short (ZAP-S) and a long form (ZAP-L). The described effects of the current investigations relate to ZAP-S. (ad)