E-Mail
The SARS-CoV-2 virus may enter and replicate in human cells by exploiting newly-identified sequences within cell receptors, according to work from two teams of scientists. The findings from both groups paint a more complete portrait of the various cellular processes that SARS-CoV-2 targets to not only enter cells, but to then multiply and spread. The results also hint that the sequences could potentially serve as targets for new therapies for patients with COVID-19, although validation in cells and animal models is needed. Scientists know that SARS-CoV-2 binds the ACE2 receptor on the surface of human cells, after which it enters the cell through a process known as endocytosis. Research has suggested that the virus may hijack or interfere with other processes such as cellular housekeeping (autophagy) by targeting other receptors called integrins. However, not much is known about exactly how the virus takes advantage of integrins on the biochemical level. Analyzing the Eukar
SARS-CoV-2: From entry to autophagy?
SARS-CoV-2, the virus that causes COVID-19, enters cells through endocytosis upon binding to the cell surface receptor ACE2 and potentially others, including integrins. Using bioinformatics, Mészáros
et al. predicted the presence of short amino acid sequences, called short linear motifs (SLiMs), in the cytoplasmic tails of ACE2 and various integrins that may engage the endocytic and autophagic machinery. Using affinity binding assays, Kliche
et al. not only confirmed that many of these predicted SLiMs interacted with target peptides in various components of the endocytosis and autophagy machinery but also found that these interactions were regulated by the phosphorylation of SLiM-adjacent amino acids. Together, these findings have identified a potential link between autophagy and integrin signaling and could lead to new ways to prevent viral infection.
SARS-CoV-2, the virus that causes COVID-19, enters cells through endocytosis upon binding to the cell surface receptor ACE2 and potentially others, including integrins. Using bioinformatics, Mészáros et al. predicted the presence of short amino acid sequences, called short linear motifs (SLiMs), in the cytoplasmic tails of ACE2 and various integrins that may engage the endocytic and autophagic machinery. Using affinity binding assays, Kliche et al. not only confirmed that many of these predicted SLiMs interacted with target peptides in various components of the endocytosis and autophagy machinery, but also found that these interactions were regulated by the phosphorylation of SLiM-adjacent amino acids. Together, these findings have identified a potential link between autophagy and integrin signaling and could lead to new ways to prevent viral infection.
The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the host cell surface and subsequently enters h