The spike glycoprotein of highly pathogenic human coronaviruses: structural insights for understanding infection, evolution and inhibition

Abstract

Highly pathogenic human coronaviruses (CoV) including SARS‐CoV, MERS‐CoV and SARS‐CoV‐2 have emerged over the past two decades, resulting in infectious disease outbreaks that have greatly affected public health. The CoV surface spike (S) glycoprotein mediates receptor binding and membrane fusion for cell entry, playing critical roles in CoV infection and evolution. The S glycoprotein is also the major target molecule for prophylactic and therapeutic interventions, including neutralizing antibodies and vaccines. In this review, we summarize key studies that have revealed the structural basis of S‐mediated cell entry of SARS‐CoV, MERS‐CoV and SARS‐CoV‐2. Additionally, we discuss the evolution of the S glycoprotein to realize cross‐species transmission from the viewpoint of structural biology. Lastly, we describe the recent progress in developing antibodies, nanobodies and peptide inhibitors that target the SARS‐CoV‐2 S glycoprotein for therapeutic purposes.

Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology

“…A multiple sequence alignment of the spike protein of each virus demonstrated that MERS-CoV showed 30.63% homology to SARS-CoV and SARS-CoV-2 displayed 76.19% homology to SARS-CoV [ 64 ]. Interestingly, the RBD SARS-CoV-2, SARS-CoVs, and MERS-CoV display a similar architecture, consisting of a β-sheet core with a twisted five-stranded antiparallel β sheet and an inserted loop that directly interact with the receptor [ 65 ]. However, SARS-CoV-2-S RBD is more structurally similar to MERS-CoV RBD than SARS-CoV RBD to MERS-CoV RBD [ 66 ].…”

Innovation and renovation: FEBS Open Bio in 2023

“…Our third special issue of the year placed the limelight firmly on one specific virus: SARS‐CoV‐2. Guest editor Alexander Wlodawer commissioned three Review articles focussing on the structures of different proteins of SARS‐CoV‐2: Robin Stanley and co‐authors discussed the structure and function of ribonucleases [ 10 ]; Franck Martin and colleagues focussed on viral and cellular translation during SARS‐CoV‐2 infection, as mediated by NSP1 [ 11 ]; and finally, Xinquan Wang, Jiwan Ge and co‐authors discussed the evolution of and therapeutic targeting of the spike glycoprotein [ 12 ].…”

SARS-CoV-2 Protein S Fusion Peptide Is Capable of Wrapping Negatively-Charged Phospholipids

“…Although new vaccines have been implemented, the pandemic goes on through the rapid evolution of different variants, and it dramatically impacts all aspects of everyone’s life. Although there are several coronaviruses (CoVs) which are relatively mild, there are, apart from SARS-CoV-2, other highly contagious β-coronaviruses which in the past have also produced pandemic outbreaks, including SARS-CoV-1 and Middle East respiratory syndrome coronavirus [ 2 ]. SARS-CoV-2 cell entry can occur in two different ways, fusion with either the plasma membrane or with the endosomal one [ 2 , 3 , 4 , 5 ].…”

“…Although there are several coronaviruses (CoVs) which are relatively mild, there are, apart from SARS-CoV-2, other highly contagious β-coronaviruses which in the past have also produced pandemic outbreaks, including SARS-CoV-1 and Middle East respiratory syndrome coronavirus [ 2 ]. SARS-CoV-2 cell entry can occur in two different ways, fusion with either the plasma membrane or with the endosomal one [ 2 , 3 , 4 , 5 ]. Membrane fusion, essential for viral entry into the host cell, has been and is one of the main targets for the development of novel antiviral therapies to combat COVID-19.…”