RT Journal Article
SR Electronic
T1 SARS-CoV-2 uses clathrin-mediated endocytosis to gain access into cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.13.201509
DO 10.1101/2020.07.13.201509
A1 Armin Bayati
A1 Rahul Kumar
A1 Vincent Francis
A1 Peter S. McPherson
YR 2020
UL http://biorxiv.org/content/early/2020/07/16/2020.07.13.201509.abstract
AB With more than 13 million cases and 570,000 deaths, and with the resulting social upheaval, the COVID-19 pandemic presents one of the greatest challenges ever to the scientific community. It is thus vital to fully understand the biology of SARS-CoV-2, the causative agent of COVID-19. SARS-CoV-2 uses the spike glycoprotein to interact with the cell surface and to drive fusion of the viral membrane with cellular membranes, thus allowing transfer of viral RNA to the cytosol. Here we use purified spike glycoprotein protein and lentivirus pseudotyped with spike glycoprotein to determine that SARS-CoV-2 undergoes rapid endocytosis following binding to the plasma membrane. Using chemical inhibitors and loss of function approaches, we demonstrate that this cellular entry is through clathrin-mediated endocytosis. Thus, it appears that SARS-CoV-2 first engages the plasma membrane, then rapidly enters the lumen of the endosomal system, strongly suggesting that fusion of the viral membrane occurs with the lumenal membrane of endosomes. This discovery has important implications for the development of chemical probes to reduce or block infection.Competing Interest StatementThe authors have declared no competing interest.