New Molecule Has Potential Anti-Herpes Virus Effect

A new molecule called BX795 appears to have an effect against herpes simplex virus-1 (HSV-1) infection of the corneal tissue of the eye. This was the finding of a study published in the Science Translational Medicine. The anti-herpes effect of the molecule BX795 was an accidental discovery. Given its mechanism of action of being a TANK-binding kinase 1 (TBK1) inhibitor, it was expected to promote the herpes virus infection; however, it produced the opposite effect when used in higher concentrations.

The scientists tested the effect of the molecule on HSV-1 infected human corneal cells cultured in the laboratory as well as intact donated human corneas and corneas of mice. The cornea is the transparent dome of the eye through which the light enters the eye. They found that:

• Higher concentrations of BX795 cleared the HSV-1 infection from the cells.
• BX795 was effective against HSV-1 viral infection that was resistant to treatment with acyclovir.
• BX795 acted only on infected cells, with no negative or side effects on the normal cells at the effective concentration.
• The combined use with another anti-HSV-1 drug trifluorothymidine (TFT) did not produce a synergistic effect.

The scientists suggest that at higher concentrations BX795 acts through a different mechanism to produce the anti-viral effect - it blocks protein synthesis by interfering with the Akt phosphorylation pathway in infected cells.

If successfully developed into a drug, BX795 will be particularly useful for those herpes infections that have developed resistance to the currently available medications. Also, given the mechanism of action of the molecule, it could also be effective against other viral infections including HIV.

The potential for the use of BX795 against HSV-1 eye infections as well as other viral infections has yet to be evaluated through extensive studies to prove its continuous effectiveness and to detect and address any drug delivery and safety concerns.

About Herpes Simplex

Herpes simplex (HSV) virus is a virus that infects the skin and mucous membranes. White the type 1 virus (HSV-1) usually affects the face including the eyes and mouth, the type 2 virus (HSV-2) is sexually transmitted and usually affects the genitals. Cases of HSV-2 infection affecting the eyes and mouth have also been reported, possibly transmitted through oral sex. The infection results in painful blisters and ulcers. Involvement of the eyes can result in blindness. Spread of the infection to the brain can result in meningoencephalitis. The herpes infection can remain latent in the nerves after the initial treatment of the infection, and re-emerge again when the immunity reduces.

The herpes infection is treated with drugs like acyclovir, valacyclovir, famciclovir, trifluorothymidine and ganciclovir. These drugs are not without side effects, and instances of resistance to the medications have been noted. There is therefore an unmet need for the development of new alternative drugs for the treatment of herpes infections, and BX795 appears to be a promising option.

Reference:

1. Jaishankar D et al. An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye. Science Translational Medicine 2018: Vol. 10, Issue 428, eaan5861 DOI: 10.1126/scitranslmed.aan5861

Source-Medindia