BX795 demonstrates potent antiviral benefits against herpes simplex Virus-1 infection of human cell lines

Antiviral Res. 2020 Aug:180:104814. doi: 10.1016/j.antiviral.2020.104814. Epub 2020 May 5.

Abstract

Herpes simplex virus-1 (HSV-1) infection is known to cause skin blisters, keratitis as well as deadly cases of encephalitis in some situations. Only a few therapeutic modalities are available for this globally prevalent infection. Very recently, a small molecule BX795 was identified as an inhibitor of HSV-1 protein synthesis in an ocular model of infection. In order to demonstrate its broader antiviral benefits, this study was aimed at evaluating the antiviral efficacy, mode-of-action, and toxicity of BX795 against HSV-1 infection of three human cell lines: HeLa, HEK, and HCE. Several different assays, including cell survival analysis, imaging, plaque analysis, Immunoblotting, and qRT-PCR, were performed. In all cases, BX795 demonstrated low toxicity at therapeutic concentration and showed strong antiviral benefits. Quite interestingly, cell line-dependent differences in the mechanism of antiviral action and cytokine response to infection were seen upon BX795 treatment. Taken together, our results suggest that BX795 may exert its antiviral benefits via cell-line specific mechanisms.

Keywords: Antiviral drug; BX795; HCE; HEK; HeLa; Herpes simplex virus-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cytokines / immunology
  • HEK293 Cells
  • HeLa Cells
  • Herpes Simplex / drug therapy
  • Herpesvirus 1, Human / drug effects*
  • Humans
  • Pyrimidines / pharmacology*
  • Thiophenes / pharmacology*

Substances

  • Antiviral Agents
  • BX795
  • Cytokines
  • Pyrimidines
  • Thiophenes