Integrin αvβ1 facilitates ACE2-mediated entry of SARS-CoV-2

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin alpha v beta 1 was highly enriched in the SARS-CoV-2 susceptible cell lines. Additional studies demonstrated that RGD (403-405)-> AAA mutant was defective in binding to integrin alpha v beta 1 compared to its wild type counterpart, and anti-alpha v beta 1 integrin antibodies significantly inhibited the entry of SARS-CoV-2 into the cells. Further studies using mouse NIH3T3 cells expressing human ACE2, integrin alpha v, integrin beta 1, and/or integrin alpha v beta 1 suggest that integrin alpha v beta 1 was unable to function as an independent receptor but could significantly facilitate the cellular entry of SASR-CoV-2. Finally, we observed that the Omicron exhibited a significant increase in the ACE2-mediated viral entry. Our findings may enhance our understanding of the pathogenesis of SARS-CoV-2 infection and offer potential therapeutic target for COVID-19.

Automated summary

This study found that integrin alpha v beta 1 is highly enriched in SARS-CoV-2 susceptible cells and can significantly facilitate viral cellular entry. Further research demonstrated that integrin alpha v beta 1 is unable to function as an independent receptor but plays an important role in the cellular entry of SASR-CoV-2. Additionally, cells expressing human ACE2 showed higher sensitivity to ACE2-mediated viral entry.