Bioinformatics analysis provides new clues for how SARS-CoV-2 cells infect

Colored scan electron micrograph of an apoptotic cell (green) heavily infested with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

The molecular details of how EARS-CoV-2 enter cells and infect it is still not clear. Researchers at Uppsala University tested the bioinformatics predictions of another research group and identified receptors that could be important role players in the process. The results are presented in the journal Science signal and during the AAAS annual meeting held this week.

The vein protein of SARS-CoV-2 binds the protein ACE2 on the outside of the human cell. It causes a series of events that lead to an invasion of the cell by the virus. The molecular details of this process have remained unclear despite much research on SARS-CoV-2 and other coronaviruses. In addition, ACE2 is not present in human lung cells, suggesting that different players are involved when the virus infects these cells.

A recent study by researchers at Uppsala University sheds new light on the issues. The study was published back-to-back with a study by an international team led by Dr Toby Gibson at the European Molecular Biology Laboratory (EMBL) in Heidelberg. The Gibson study predicts potential interactions that may be important for the entry of Sars-CoV-2 into the cell.

The researchers at Uppsala University tested the bioinformatics predictions in vitro and were able to show that ACE2 and the potential co-receptor integrins beta3 interact with important players involved in endocytosis and autophagy – cellular processes of uptake and disposal of substances. This means that these processes can be hijacked by the virus during infection.

“The Gibson team is at the forefront of bioinformatics analysis of these types of interactions, and we were excited to follow up on their predictions,” said Professor Ylva Ivarsson, head of the Uppsala study. “Our results also helped them to improve their analysis. It was an easy decision to participate in this project as our laboratory has a strong interest in host-pathogen protein-protein interactions. ”

Reference: “Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host receptors to mediators of endocytosis and autophagy” by Johanna Kliche, Hanna Kuss, Muhammad Ali and Ylva Ivarsson, 12 January 2021, Science signal.
DOI: 10.1126 / scisignal.abf1117

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