title: A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2.
abstract: In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide (438)YKYRYL(443) is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. (438)YKYRYL(443) carries the dominant binding epitope and binds to ACE2 with K(D)=46 μM. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses.
authors.affiliation: Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin Luther King Place 6, 20146 Hamburg, Germany.
authors.forename: Anna-Winona
authors.initials: AW
authors.lastname: Struck
authors.forename: Marco
authors.initials: M
authors.lastname: Axmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Pfefferle
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.forename: Bernd
authors.initials: B
authors.lastname: Meyer
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D064370:Spike Glycoprotein, Coronavirus; D020349:Surface Plasmon Resonance; D014759:Viral Envelope Proteins / Q000235:genetics / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D008562:Membrane Glycoproteins; D010455:Peptides; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2