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.
Highlights
Conventional antiviral drugs (AVs) that interfere with viral proteins or functions have been developed against a number of different animal viral diseases, but these compounds often lead to selection of drug resistance in virus populations evolving under selective pressures (Cuypers et al, 2016; Maldonado and Mansky, 2018)
We have previously demonstrated that viral production was strongly inhibited at non-toxic concentrations of lauryl gallate (LG), in different cell lines infected with African swine fever virus (ASFV), herpes simplex virus (HSV-1), vaccinia virus (VV), influenza virus, transmissible gastroenteritis virus and Sindbis virus (Hurtado et al, 2008)
Direct virucidal effect of the AVs selected for this study in ASFV or foot and mouth disease virus (FMDV) infections was assayed by incubation of virus samples for 1 h at room temperature with increasing concentrations of the drugs
Summary
Conventional antiviral drugs (AVs) that interfere with viral proteins or functions have been developed against a number of different animal viral diseases, but these compounds often lead to selection of drug resistance in virus populations evolving under selective pressures (Cuypers et al, 2016; Maldonado and Mansky, 2018). An efficient non-conventional cell-targeted antiviral would inhibit viral entry and/ or replication at a non-toxic concentration for the cell and, ideally, it would help to control a wide variety of viral diseases and virus strains. Following this approach, we have focused our studies on three compounds: lauryl gallate (LG), valproic acid (VPA), and cerulenin (CRL). Due to its hydrophobic properties, LG can disrupt biomembranes and cause protein inactivation (Jurak and Minones, 2016) This interaction with lipid molecules can be correlated with different pharmacological effects against bacterial cells and viruses (Ogita et al, 2004; Hurtado et al, 2008).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
