Proteolysis of Sars-Associated Coronavirus Spike Glycoprotein

摘要: Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) mediates attachment, receptor engagement and entry via its spike glycoprotein (S). S-dependent viral requires the presence of a primary receptor, angiotensin converting enzyme-2 (ACE2), while C-type lectins, DC-SIGN, DC-SIGNR, LSECtin act as attachment factors, promoting binding to subset target cells. SARS-CoV S, like other glycoproteins, contains two leucine/ isoleucine heptad repeats (HR1 HR2) located in C-terminal third glycoprotein. By homology fusion proteins, such influenza hemagglutinin (HA) HIV gp160, HR1 HR2 are thought drive membrane through their interaction together. from each member trimeric pack together form highly stable structure known six-helix bundle. The events following leading up bundle formation less defined. Viral mediated by S is exquisitely sensitive compounds able raise pH cellular endosomes. Thus, pH-dependent component appears be required for cell-free infection S. However, cell-to-cell can occur at neutral pH, furthermore not enhanced acidic pH. Therefore, it unlikely that has direct requirement conditions order undergo conformational rearrangements formation, seen proteins HA. In contrast, when cells expressing endogenous, low levels ACE2 were used targets cellto-cell fusion, treatment effectors with trypsin necessary efficient observed. we hypothesize virus occur, similar proteolytic activity required, mimics protease, hence explaining sensitivity endosomal