Biology subjects

Petrov, F.

Publications and source records attributed to Petrov, F..

2 recordsLinked to original sources

bioRxiv2026

Inhibition of VP2-mediated entry: a potential antiviral strategy to treat or prevent calicivirus disease

The Caliciviridae include many notable human and animal pathogens, including norovirus and sapovirus, which cause outbreaks of acute gastroenteritis. We previously demonstrated that, following receptor engagement, feline calicivirus (FCV) assembles a portal structure at a unique capsid three-fold axis. This comprises twelve copies of the minor capsid protein VP2 and is essential for genome delivery. We designed a short peptide based on our structure data that occludes the VP2 binding sites on the capsid surface, to prevent assembly of the VP2 portal and thereby halt the viral entry mechanism. Incubation with low micromolar concentrations of the peptide considerably reduced the infectivity of two laboratory strains and four clinical isolates of FCV associated with respiratory or virulent-systemic disease. Cryo-electron microscopy structures of FCV virions complexed with the peptide confirmed that the peptide occupies the VP2 binding site on the major capsid protein VP1, preventing portal assembly and subsequent genome delivery. Our data show that targeting VP2 is a viable antiviral approach to preventing calicivirus infection, with potential for the treatment or prevention of norovirus disease.

microbiology↗

bioRxiv2026

Cryo-EM of a Divergent Herpesvirus Reveals Structural Conservation and Novelty Including a Portal-Vertex Tegument Protein with Multiple Macrodomain-like Folds

Ictalurid herpesvirus 1 (channel catfish virus) is an evolutionarily distant relative of human herpesviruses, from which it is thought to have diverged >400M years ago. Using cryogenic electron microscopy (cryo-EM) combined with symmetry-breaking and particle subtraction approaches, we determined structures of both the immature capsid and virion of IcHV-1. Due to limited genome annotation, we used the machine learning-based tool ModelAngelo for de novo model building, enabling unambiguous protein identification even at marginal resolutions. Notably, the IcHV-1 virion was found to have a substantial and elaborate portal-vertex associated tegument (PVAT) complex. Overall, we determined the identities and structures of ten IcHV-1 proteins: the major capsid protein; the triplex proteins; two novel virion-associated inner tegument proteins; the portal protein; and a further four PVAT proteins. Our findings reveal a high degree of fold conservation in the core capsid proteins when compared with those of human herpesviruses, but also considerable structural novelty, including for the first time in a herpesvirus, identification of a protein that has four putative macrodomains.

microbiology↗