LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3. We have analysed several nucleoside analogs and recombinant IFN-α2 to determine which combinations have increased anti-herpes simplex virus type 1 (HSV) activity. The questions we are addressing: (1) How does the vhs protein specifically target mRNA for degradation, but not rRNA or tRNA, in infected cells? N-MCT inhibited KSHV virion production in lytically induced KSHV-infected BCBL-1 cells with a substantially lower 50% inhibitory concentration (IC50) than those of cidofovir (CDV) and ganciclovir (GCV) (IC50, mean ± standard deviation: 0.08 ± 0.03, 0.42 ± 0.07, and 0.96 ± 0.49 μM for N-MCT, CDV, and GCV, respectively). The compound is also effective in vivo and reduces the mortality of mice infected with orthopoxviruses, as well as those infected with herpes simplex virus type 1 when treatment is initiated 24 h after infection. In a herpes type 2 infection model in mice, DHPG, and FMAU were active at 5 mg/kg, whereas acyclovir and FIAC showed no statistically significant effect at 80 mg/kg. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect.
The binding mode of (+)-rutamarin to the ATPase domain of human Topo IIα was established by docking and validated by molecular dynamics (MD) simulations. In conclusion, the present study demonstrated that Pa-MAP seems to be a reliable candidate for a possible alternative drug to treat HSV-1 infections. This article is protected by copyright. All rights reserved.