Coronavirus disease 2019 (COVID-19) is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is broadly accepted that SARS-CoV-2 utilizes its spike protein to recognize the extracellular domain of angiotensin-converting enzyme 2 (ACE2) to enter cells for viral infection. However, other mechanisms of SARS-CoV-2 cell entry may occur. We show quantitatively that the SARS-CoV-2 spike protein also binds to the extracellular domain of broadly expressed integrin α5β1 with an affinity comparable to that of SARS-CoV-2 binding to ACE2. More importantly, we provide direct evidence that such binding promotes the internalization of SARS-CoV-2 into non-ACE2 cells in a manner critically dependent upon the activation of the integrin. Our data demonstrate an alternative pathway for the cell entry of SARS-CoV-2, suggesting that upon initial ACE2-mediated invasion of the virus in the respiratory system, which is known to trigger an immune response and secretion of cytokines to activate integrin, the integrin-mediated cell invasion of SARS-CoV-2 into the respiratory system and other organs becomes effective, thereby promoting further infection and progression of COVID-19.
【저자키워드】 COVID-19, SARS-CoV-2, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, ACE2, angiotensin-converting enzyme 2, virus infection, RBD, receptor binding domain, integrin, SPR, surface plasmon resonance, hACE2, human ACE2, Cy5-RBD, cyanine5-labeled RBD, HBSS, Hanks' banlanced salt solution, R403GD, arginine–glycine–aspartic acid,