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.
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.
Bosch
Berend Jan
BJ
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.
Rossen
John W A
JW
Bartelink
Willem
W
Zuurveen
Stephanie J
SJ
de Haan
Cornelis A M
CA
Duquerroy
Stephane
S
Boucher
Charles A B
CA
Rottier
Peter J M
PJ
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
D008562:Membrane Glycoproteins; D010455:Peptides; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins