Putative targeting by BX795 causes decrease in protein kinase C protein levels and inhibition of HSV1 infection

Rahul K. Suryawanshi, Chandrashekhar D. Patil, David Wu, Pritam Kumar Panda, Sudhanshu Kumar Singh, Ipsita Volety, Rajeev Ahuja, Yogendra Kumar Mishra, Deepak Shukla

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Herpes simplex virus type-1 (HSV1) exploits cellular machinery for its own replicative advantage. Current treatment modalities against HSV1 cause toxicity and drug resistance issues. In the search for alternative forms of treatment, we have uncovered a small molecule, BX795, as a candidate drug with strong antiviral potential owing to its multitargeted mode of action. In this study, we show that in addition to a previously known mechanism of action, BX795 can directly interact with the proviral host factor protein kinase C (PKC) in silico. When administered to HSV1 or mock infected human corneal epithelial (HCE) cells, BX795 significantly reduces the protein level and perinuclear localization of proviral PKC-α and PKC-ζ isoforms. This activity closely mimics that of a known PKC inhibitor, Bisindolylmaleimide I (BIM I), which also inhibits viral replication. Taken together our studies demonstrate a previously unknown mechanism by which BX795 exerts its antiviral potential.

Original languageEnglish
Article number105454
JournalAntiviral Research
Volume208
DOIs
StatePublished - 1 Dec 2022
Externally publishedYes

Keywords

  • Antiviral
  • BX795
  • Herpesvirus
  • Mechanism
  • Protein kinase C

ASJC Scopus subject areas

  • Virology
  • Pharmacology

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