The Valproic Acid Derivative Valpromide Inhibits Pseudorabies Virus Infection in Swine Epithelial and Mouse Neuroblastoma Cell Lines

Abstract

Pseudorabies virus (PRV) infection of swine can produce Aujeszky’s disease, which causes neurological, respiratory, and reproductive symptoms, leading to significant economic losses in the swine industry. Although humans are not the natural hosts of PRV, cases of human encephalitis and endophthalmitis caused by PRV infection have been reported between animals and workers. Currently, a lack of specific treatments and the emergence of new PRV strains against which existing vaccines do not protect makes the search for effective antiviral drugs essential. As an alternative to traditional nucleoside analogues such as acyclovir (ACV), we studied the antiviral effect of valpromide (VPD), a compound derived from valproic acid, against PRV infection in the PK15 swine cell line and the neuroblastoma cell line Neuro-2a. First, the cytotoxicity of ACV and VPD in cells was compared, demonstrating that neither compound was cytotoxic at a specific concentration range after 24 h exposure. Furthermore, the lack of direct virucidal effect of VPD outside of an infected cell environment was demonstrated. Finally, VPD was shown to have an antiviral effect on the viral production of two strains of pseudorabies virus (wild type NIA-3 and recombinant PRV-XGF) at the concentrations ranging from 0.5 to 1.5 mM, suggesting that VPD could be a suitable alternative to nucleoside analogues as an antiherpetic drug against Aujeszky’s disease.

Brincidofovir Effectively Inhibits Proliferation of Pseudorabies Virus by Disrupting Viral Replication

“…Hydroquinone and adefovir dipivoxil, which are listed in the FDA-approved drug library, were found to have a significant antiviral effect in vitro and in vivo against classical PRV strains, while the effects against the variant PRV strains and human-origin strains are unclear [ 21 , 22 ]. Although the valproic acid derivative valpromide (VPD) could inhibit PRV proliferation in PK-15 and Neuro-2a cells in the concentration range of 0.5 to 1.5 mM, no data support its medicative effect in vivo [ 35 ]. Ivermectin, an antiparasitic drug, also exhibited 100% inhibition of PRV replication at 2.0 μM in vitro and reduced mortality by 50% in PRV-infected mice with attenuated brain damage [ 23 ].…”

Pseudorabies virus uses clathrin mediated endocytosis to enter PK15 swine cell line

“…PRV-XGF-N was obtained by replacing the gene encoding the PRV gG glycoprotein (glycoprotein that is not part of the virion as it is secreted into the medium by infected cells, being not essential for virulence) with the EGFP gene in NIA-3 wild type PRV strain. PRV-XGF-N was propagated and titrated with a 50% tissue culture infective dose (TCID 50 ) assay in PK15 cells as previously described ( Andreu et al, 2021 ).…”

Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo

“…This virus was propagated on Huh-7 cells for 5 days at 33°C with 5% CO 2 . The infectious titer of the virus stocks was determined according to the Reed and Muench formula (Reed and Muench, 1938 ) on Huh-7 cell monolayers by the endpoint dilution assay described in Andreu et al ( 2021 ). HSV-1 K26-GFP (a kind gift from.…”