title: Coronavirus escape from heptad repeat 2 (HR2)-derived peptide entry inhibition as a result of mutations in the HR1 domain of the spike fusion protein.
abstract: Peptides based on heptad repeat (HR) domains of class I viral fusion proteins are considered promising antiviral drugs targeting virus cell entry. We have analyzed the evolution of the mouse hepatitis coronavirus during multiple passaging in the presence of an HR2-based fusion inhibitor. Drug-resistant variants emerged as a result of multiple substitutions in the spike fusion protein, notably within a 19-residue segment of the HR1 region. Strikingly, one mutation, an A1006V substitution, which consistently appeared first in four independently passaged viruses, was the main determinant of the resistance phenotype, suggesting that only limited options exist for escape from the inhibitory effect of the HR2 peptide.
authors: Virology Division, Department of Infectious Diseases and Immunology, Utrecht University, Faculty of Veterinary Medicine, and Institute of Biomembranes, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
authors: Berend Jan
authors: BJ
authors: Bosch
authors: John W A
authors: JW
authors: Rossen
authors: Willem
authors: W
authors: Bartelink
authors: Stephanie J
authors: SJ
authors: Zuurveen
authors: Cornelis A M
authors: CA
authors: de Haan
authors: Stephane
authors: S
authors: Duquerroy
authors: Charles A B
authors: CA
authors: Boucher
authors: Peter J M
authors: PJ
authors: Rottier
mesh_terms: D000818:Animals; D002460:Cell Line; D017934:Coronavirus / Q000502:physiology*; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D051379:Mice; D009154:Mutation; D010455:Peptides / Q000502:physiology*; D020449:Repetitive Sequences, Amino Acid; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology
chemical_list: D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins