Inhibition of Porcine Viruses by Different Cell-Targeted Antiviral Drugs

Abstract

Antiviral compounds targeting cellular metabolism instead of virus components have become an interesting issue for preventing and controlling the spread of virus infection, either as sole treatment or as a complement of vaccination. Some of these compounds are involved in the control of lipid metabolism and/or membrane rearrangements. Here, we describe the effect of three of these cell-targeting antivirals: lauryl gallate (LG), valproic acid (VPA), and cerulenin (CRL) in the multiplication of viruses causing important porcine diseases. The results confirm the antiviral action in cultured cells of LG against African swine fever virus (ASFV), foot and mouth disease virus (FMDV), vesicular stomatitis virus (VSV), and swine vesicular disease virus (SVDV), as well as the inhibitory effect of VPA and CRL on ASFV infection. Other gallate esters have been also assayed for their inhibition of FMDV growth. The combined action of these antivirals has been also tested in ASFV infections, with some synergistic effects when LG and VPA were co-administered. Regarding the mode of action of the antivirals, experiments on the effect of the time of its addition in infected cell cultures indicated that the inhibition by VPA and CRL occurred at early times after ASFV infection, while LG inhibited a late step in FMDV infection. In all the cases, the presence of the antiviral reduced or abolished the induction of virus-specific proteins. Interestingly, LG also reduced mortality and FMDV load in a mouse model. The possible use of cell-targeted antivirals against porcine diseases is discussed.

Inhibition of Human Coronaviruses by Combinations of Host-Targeted and Direct-Acting Antivirals

“…We previously described the efficient inhibition of virus multiplication in several cell lines in the presence of a host-targeted AV, the antioxidant food additive LG ( 19 , 20 ). We also demonstrated that VPA, another drug affecting cellular functions, used for treatment of neurological disorders, caused a drastic reduction in replication of all enveloped viruses tested ( 24 , 25 ).…”

“…Esters of G have also been reported to inhibit the proliferation of tumoral cell lines ( 13 ) by triggering the apoptosis of the cell ( 14 ) and the concomitant inhibition of protein tyrosine kinases ( 15 ) and have been described as AVs ( 16 – 18 ). We have previously reported that LG can inhibit the replication in cultured cells of African swine fever virus (ASFV), foot-and-mouth disease virus (FMDV), herpesvirus simplex (HSV-I), influenza virus, Sindbis virus (SINV), vaccinia virus (VACV), vesicular stomatitis virus (VSV), swine vesicular disease virus (SVDV), and transmissible gastroenteritis virus (TGEV), also reducing mortality and FMDV load in vivo in a mouse model ( 19 , 20 ). The antiviral effect of LG might be mediated by its interaction with phospholipids in biological membranes ( 21 ), with surfactant effects destabilizing the cellular and viral envelopes.…”

A new microtubule-stabilizing agent shows potent antiviral effects against African swine fever virus with no cytotoxicity

“…Therefore, much effort has been made to discover and study antiviral agents against ASFV [42][43][44][45][46][47]. However, none of the described compounds have been tested in vivo yet, thereby highlighting the need to search for new antiviral agents targeted towards the ASFV.…”

“…Indeed, the 4D docking experiments and MD simulations revealed that this compound could interact with the taxane site in the same manner as many other microtubules stabilizing agents [50]. Ethyl [(4-cyano-1-phenyl-5,6,7,8-tetrahydroisoquinolin-3-yl) The immunostaining of ASFV-pI215L and ASFV-infected cells were achieved by incubation with two in-house primary antibodies: mouse anti-ASFV-PI215L and anti-ASFV swine serum directly conjugated to fluorescein isothiocyanate (FITC; 1:100, 1 h, RT) as previously described [47,48]. The affinity purified Alexa Fluor 568-conjugated goat anti-mouse secondary antibody In some experiments, ASFV-infected cells were exposed to EdU (5-ethynyl-2′-deoxyuridine; 25 microM) for 15 min before collection; cells exposed to solvent (DMSO) served as controls.…”

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

“…An alternative that remains under study is valproic acid (VPA) [26], a branched, shortchain fatty acid used in the treatment of seizure disorders [27]. Numerous studies have proven that VPA interferes with the infectious cycle of several enveloped viruses, including herpesviruses, flaviviruses, arenaviruses, poxviruses, picornaviruses, rhabdoviruses, and coronaviruses, among others [28][29][30][31][32][33]. However, VPA shows hepatotoxic and teratogenic activity [34], and thus to reduce these deleterious effects, derivatives of VPA have been tested.…”