Protein sequences provide insight to SARS-CoV-2 infection, study shows

Research has shown that ACE2 and several integrins containing SLiMs are involved in SARS-CoV-2 infection, presenting new therapeutic targets.

SARS-CoV-2 infection

Researchers have analysed sequences of angiotensin-converting enzyme 2 (ACE2) and other human proteins involved in SARS-CoV-2 infection. The study was conducted at the European Molecular Biology Laboratory (EMBL), in collaboration with the Universidad Nacional de San Martín, Argentina, and partners from Merck KGaA Darmstadt and University College Dublin, Ireland. 

According to the team, other proteins involved in SARS-CoV-2 infection include a class of proteins called integrins. The researchers focused on short strings of amino acids called short linear motifs (SLiMs), which are involved in transmitting information between the inside and outside of cells. 

They saw that ACE2 and several integrins contain SLiMs that are probably involved in endocytosis and autophagy – cellular processes of uptake and disposal of substances, respectively. This result suggests previously unknown roles of ACE2 and integrins in cell physiology.

“If SARS-CoV-2 targets proteins involved in endocytosis and autophagy, it means these processes might be hijacked by the virus during infection,” said Bálint Mészáros, a postdoc at EMBL and the first author of the study.

The researchers say that the findings might lead to new therapeutic approaches for COVID-19. “SLiMs could ‘switch’ to turn viral entry signals on or off. This means that if we can find a way to reverse these switches using drugs, this might stop coronavirus from entering cells,” said senior author Lucía Chemes from the Universidad Nacional de San Martín. 

The team gathered a list of existing drugs that interfere with endocytosis and autophagy. The list includes candidates such as the antipsychotic chlorpromazine.

The results of the study are published in Science Signaling