WASHINGTON: Other details study with the American Society for the Advancement of Science states that the SARS-CoV-2 virus not only targets the entry of human cells but also begins to reproduce and spread.
The findings also clarify that the opportunities may be targets for new treatments for patients with COVID-19, although confirmation is needed in both cell and animal models. 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 called endocytosis.
Research has suggested that the virus may trap or inhibit other processes such as cell retention (autophagy) by targeting other receptors called integrins. However, little is known about just how the virus exploits integrins at the biochemical level. Analyzing the Eukaryotic Linear Motif database, Balint Meszaros and colleagues found that ACE2 contained several short series motifs (SLiMs) and various integrins – small amino acid sequences – that they were expected to play a role in endocytosis and autophagy.
The scientists then compiled a list of currently used experimental therapies and approved drugs that could target the interactions between SARS-CoV-2 and its target SLiMs. Separately, Johanna Kliche and colleagues performed molecular experiments to see if these SLiMs interacted with proteins that contribute to autophagy and endocytosis.
The team found that two SLiMs in ACE2 were bound to the endocytosis proteins SNX27 and SHANK, and one SLiM in the Beta-3 integrin bound to two proteins involved in autophagy. In addition to providing a replacement drug replacement drug for SARS-CoV-2, Meszaros et al. say that their predictive methods could help identify similar sub-radar SLiMs that help reproduce other disease-causing viruses.
The findings also clarify that the opportunities may be targets for new treatments for patients with COVID-19, although confirmation is needed in both cell and animal models. 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 called endocytosis.
Research has suggested that the virus may trap or inhibit other processes such as cell retention (autophagy) by targeting other receptors called integrins. However, little is known about just how the virus exploits integrins at the biochemical level. Analyzing the Eukaryotic Linear Motif database, Balint Meszaros and colleagues found that ACE2 contained several short series motifs (SLiMs) and various integrins – small amino acid sequences – that they were expected to play a role in endocytosis and autophagy.
The scientists then compiled a list of currently used experimental therapies and approved drugs that could target the interactions between SARS-CoV-2 and its target SLiMs. Separately, Johanna Kliche and colleagues performed molecular experiments to see if these SLiMs interacted with proteins that contribute to autophagy and endocytosis.
The team found that two SLiMs in ACE2 were bound to the endocytosis proteins SNX27 and SHANK, and one SLiM in the Beta-3 integrin bound to two proteins involved in autophagy. In addition to providing a replacement drug replacement drug for SARS-CoV-2, Meszaros et al. say that their predictive methods could help identify similar sub-radar SLiMs that help reproduce other disease-causing viruses.