How coronavirus interacts with human cell proteins

Scientists created the first global atlas of direct interactions between SARS-CoV-2 RNA and the human cell proteins

Scientists have charted the first atlas showing how the genetic material of the novel coronavirus interacts with the proteins in human cells, which may provide a starting point for the development of new treatments against COVID-19.

According to the researchers, one of the most urgent tasks is to understand all the molecular interactions between the virus and the cells it infects.

They explained that a detailed understanding of these interactions will help identify the processes in host cells which favour the multiplication of the virus, and the ones which activate the host immune system.

While the SARS-CoV-2 virus uses host proteins to replicate, the scientists said until now, there has been no detailed understanding of all the proteins occurring in human cells which interact with the viral genetic material – its RNA.

In the research, published in the journal Nature Microbiology, the scientists created the first global atlas of direct interactions between the SARS-CoV-2 RNA and the proteins present in human cells.

Based on the findings, the researchers also identified important regulators of viral replication.

The scientists infected human cells with the novel coronavirus, purified the viral RNA and identified the proteins bound to it.

“In this particular case, we were able to perform quantitative measurements to identify the strongest specific binding partners,” said study co-author Mathias Munschauer from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Germany.

The scientists said the atlas of RNA–protein interactions offers unique insights into SARS-CoV-2 infections, enabling the systematic breakdown of factors influencing the replication of the virus, and host defense strategies – a crucial prerequisite for the development of new therapeutics.

From the results, the scientists identified 18 host proteins that play an important role during SARS-CoV-2 infection, and found 20 small molecules that may inhibit these proteins.

They believe the two proteins CNBP and LARP1 are particularly interesting.

The researchers also identified target sites in these proteins that could be used to inhibit its replication.

According to Munschauer, the characterization of LARP1 as an antiviral factor is a major finding.

“The way LARP1 binds to viral RNA is very interesting, because it is similar to the way LARP1 regulates certain cellular messenger RNAs that we already know. This in turn provides insights into possible mechanisms of action,” he added.

According to the scientists, three out of four small molecules they tested inhibited viral replication in different human cell types – findings that may open up new ways to treat COVID-19.

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