Amidic derivatives of valproic acid, valpromide and valnoctamide, inhibit HSV-1 infection in oligodendrocytes

Hsv-1 Endocytic Entry into a Human Oligodendrocytic Cell Line Is Mediated by Clathrin and Dynamin but Not Caveolin

“…Genomic DNA contamination was assessed by amplification of representative samples without real team (RT) enzyme. Real-time quantitative RT-PCR assays were performed as previously described [26,27] with primer sequences targeting the immediate early gene ICP4 and early gene polymerase (Pol) and analyzed by the Genomics Core Facility at Centro de Biología Molecular Severo Ochoa (CSIC-UAM). In order to find the most suitable genes for normalization, the stability of three candidates-Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), 18S and ubiquitin (UBQ)-was analyzed with the NormFinder algorithm.…”

Valproic Acid and Its Amidic Derivatives as New Antivirals against Alphaherpesviruses

“…VPD was tested at 0.5 mM, a concentration compatible with the therapeutic doses already approved in humans. Indeed, OPCs viability in the presence of 0.5 mM VPD during 24 h was close to 100% [49]. These promising results encourage testing VPD antiviral activity in animal models and possibly in human clinical trials.…”

“…The most important described teratogenic effects for VPA are major congenital malformations and neural tube defects in embryo and fetus, and thus is not recommended for women of childbearing age [46,47]. This teratogenicity is achieved through its structural characteristics: having a carboxylic acid, branching in carbon atom 2 (C-2) with two side chains, each containing at least three carbon atoms, and presenting a hydrogen atom at C-2 [48] Regarding hepatotoxicity, it is suggested that VPA metabolism leads to two hepatotoxic metabolites (4-ene-VPA and 2,4-diene-VPA), which may form an intermediate thioester with the free form of the mitochondrial coenzyme A in the liver [49,50]. Another hypothesis proposed that the hepatotoxicity associated with VPA originates from the inhibition of pyruvate transport, ATPand GTP-dependent succinate-CoA ligases, hepatic N-acetylglutamate synthase and α-lipoamide dehydrogenase [51].…”

Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

“…12 This molecule has also shown intrinsic antiviral activity probably due to its activity as histone deacetylase inhibitor. 9,[13][14][15][16] VPA has shown anti-inflammatory activity in myocardial 17 as well as neural tissue in models of brain and spinal cord injuries, 18,19 although with some conflicting findings. 20 Although long-term adverse effects and even pro-inflammatory consequences have been reported with the chronic use of VPA, 12 we believe that, given the urgent need to have .…”

“…12 This molecule has also shown intrinsic antiviral activity probably due to its activity as histone deacetylase inhibitor. 9,13–16 VPA has shown anti-inflammatory activity in myocardial 17 as well as neural tissue in models of brain and spinal cord injuries, 18,19 although with some conflicting findings. 20…”