How Coronavirus Interacts with Cells

Characterizing SARS-CoV-2 interactions can improve understanding of viral RNA functions and the host innate immune response.

SARS-CoV-2, the virus which causes the coronavirus disease 2019 (COVID-19), is currently the leading threat to human health across the globe. Gaining a thorough understanding of how the disease interacts with the cells it infects is a key question needing answers in order to help potentially end the ongoing pandemic. Whether the molecular interactions enable the multiplication of the virus or not needs clarification, and much research is being conducted to ascertain this.

The SARS-CoV-2 virus uses the host cells proteins to multiply and spread itself, however, so far there has been no detailed information gathered on the human proteome, or the total number of all proteins that occur in human cells, that are in direct contact with existing viral RNA.

A team of collaborative investigators from the Helmholtz Institute for RNA-based Infection Research (HIRI) Würzburg, the Julius-Maximilians-Universität Würzburg (JMU) and the Broad Institute in Cambridge, Massachusetts, have now successfully created the world’s first map of the interactions between the virus and the human proteome.

For the study, which was published in Nature Microbiology, the team of investigators infected human cells with the SARS-CoV-2 virus and purified the viral RNA to identify the proteins that were connected to it. In total, they identified 18 host proteins that seem to play a principal role throughout the infection.

"The atlas of RNA-protein interactions created in this way offers unique insights into SARS-CoV-2 infections and enables the systematic breakdown of central factors and defense strategies, a crucial prerequisite for the development of new therapeutic strategies," Jochen Bodem, a co-author on the study said.

Using genetic tools, the investigators identified the exact binding sites of two host proteins, called CNBP and LARP1, and saw that they explicitly inhibited the virus’ ability to replicate. The finding of the antiviral properties of these proteins is an important discovery due to the fact that it gives insights into potential mechanisms of action.

“Our work highlights opportunities for targeting proteins or pathways linked to the SARS-CoV-2 RNA interactome to interfere with viral infection,” the authors wrote. “We believe that our approach provides a general roadmap for dissecting the biology of RNA viruses and the interactions between hosts and pathogens at the molecular level.”