Effect of fatty acids on arenavirus replication: inhibition of virus production by lauric acid

Abstract

To study the functional involvement of cellular membrane properties on arenavirus infection, saturated fatty acids of variable chain length (C10-C18) were evaluated for their inhibitory activity against the multiplication of Junin virus (JUNV). The most active inhibitor was lauric acid (C12), which reduced virus yields of several attenuated and pathogenic strains of JUNV in a dose dependent manner, without affecting cell viability. Fatty acids with shorter or longer chain length had a reduced or negligible anti-JUNV activity. Lauric acid did not inactivate virion infectivity neither interacted with the cell to induce a state refractory to virus infection. From mechanistic studies, it can be concluded that lauric acid inhibited a late maturation stage in the replicative cycle of JUNV. Viral protein synthesis was not affected by the compound, but the expression of glycoproteins in the plasma membrane was diminished. A direct correlation between the inhibition of JUNV production and the stimulation of triacylglycerol cell content was demonstrated, and both lauric-acid induced effects were dependent on the continued presence of the fatty acid. Thus, the decreased insertion of viral glycoproteins into the plasma membrane, apparently due to the increased incorporation of triacylglycerols, seems to cause an inhibition of JUNV maturation and release.

Antimicrobial Effects of Virgin Coconut Oil and Its Medium-Chain Fatty Acids onClostridium difficile

“…[30][31][32] VCO and several of its constituent fatty acids: lauric, capric, and caprylic acid have been shown in other studies to inhibit the growth of microbes, including enveloped viruses, yeast (e.g., C. albicans), and bacteria (e.g., C. perfringens). 11,12,[14][15][16]18,23,33 VCO, when consumed, would be digested by lipases of the digestive tract, releasing the individual fatty acids and ultimately inhibiting the growth of microorganisms in vivo. 34 C. difficile lacks lipases to digest coconut oil, 35,36 requiring the oil to be lipolyzed with porcine lipase before evaluating its effect in vitro.…”

Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds

“…In recent years, several natural and synthetic products have been reported as active in vitro inhibitors against arenavirus infection. The compounds under study include steroids (Wachsman et al, 2000), polysulfates (Andrei & De Clercq, 1990;Witvrouw et al, 1994), thiosemicarbazones (García et al, 2003a), trichothecenes (García et al, 2002b), phenothiazines (Candurra et al, 1996), fatty acids and analogues (Cordo et al, 1999;Bartolotta et al, 2001) and peptides (Castilla et al, 1998;Albiol Matanic & Castilla, 2004). Recent research on antiviral strategies against LCMV also describes the potential application of certain nucleoside analogues for increased mutagenesis (Grande-Pérez et al, 2005), as well as the downregulation of gene expression produced by small interfering RNAs (Sánchez et al, 2005).…”

Induction of Apoptosis by the Medium-Chain Length Fatty Acid Lauric Acid in Colon Cancer Cells due to Induction of Oxidative Stress

“…To date, few studies have investigated the apoptotic properties of lauric acid. However, published literature has reported that lauric acid exerts antimicrobial effects by inhibiting growth or reducing cell viability in bacterial and viral species [36,37,38]. …”