Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein

Abstract

The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S 1 /S 2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-.

COVID-19: Epidemiology, Evolution, and Cross-Disciplinary Perspectives

“…Interestingly, S of 2019-nCoV has acquired a polybasic motif at the S1/S2 boundary, which is not present in S of the bat CoVs and SARS-CoV [68]. Preliminary data showed that S of 2019-nCoV is cleaved by furin during its biosynthesis [69]. This is reminiscent of low-pathogenic avian influenza viruses, which, if introduced into a poultry farm, may acquire a polybasic cleavage motif that causes a deadly outbreak of highly…”

Structural and functional analysis of a potent sarbecovirus neutralizing antibody

“…1a-b) . MAbs were further evaluated for binding to the SARS-CoV-2 and SARS-CoV S B domains as well as to the prefusion-stabilized OC43 S 28 , MERS-CoV S 29,30 , SARS-CoV S 30 and SARS-CoV-2 S 6 ectodomain trimers. None of the mAbs studied bound to prefusion OC43 S or MERS-CoV S ectodomain trimers, indicating a lack of cross-reactivity outside the sarbecovirus subgenus (Extended Data Fig.1) .…”

“…SARS-CoV-2 S is closely related to the bat SARS-related CoV (SARSr-CoV) RaTG13 with which it shares 97.2% amino acid sequence identity 1 . We and others recently demonstrated that human angiotensin converting enzyme 2 (hACE2) is a functional receptor for SARS-CoV-2, as is the case for SARS-CoV 1,6-8 . The S domain B (S B ) is the receptor binding domain (RBD) and binds to hACE2 with high-affinity, possibly contributing to the current rapid SARS-CoV-2 transmission in humans 6,9 , as previously proposed for SARS-CoV 10 .…”

“…The S trimers are extensively decorated with N-linked glycans that are important for protein folding 11 and modulate accessibility to host proteases and neutralizing antibodies 12-15 . Cryo-electron microscopy (cryoEM) structures of SARS-CoV-2 S in two distinct functional states 6,9 along with cryoEM and crystal structures of SARS-CoV-2 S B in complex with hACE2 16-18 revealed dynamic states of S B domains, providing a blueprint for the design of vaccines and inhibitors of viral entry.…”

Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), family Coronaviridae , genus Betacoronavirus , is spreading widely in China, causing coronavirus disease 2019 (COVID-19)(1). Since 2003, three Coronaviruses have been associated with pneumonia, the first was severe acute respiratory syndrome coronavirus (SARS-CoV)(2) which affected 8,098 people causing 774 deaths between 2002 and 2003(3), the second was Middle-East respiratory syndrome coronavirus (MERS-CoV)(4) which affected 27 countries and infecting a total of 2,494 individuals and claiming 858 lives(4). SARS-CoV-2 is a human pathogen which has been declared a global pandemic by the World Health Organisation (5).…”