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Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications

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.

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