**Author details**

306 Lipid Metabolism

[202].

[207].

**4. Conclusion** 

described for AiV [108,122]. In this way, modulation of the interaction between these

In HCV infection the isoform of the enzyme involved in viral replication is mainly PI4KIIIα [106,107], although a role of the β isoform in the inhibition of HCV replication due to treatment with PIK93 has also been reported [126]. Consistent with these findings, specific compounds that successfully inhibit PV replication through blockage of PI4KIIIβ (GW5074 and T-00127-HEV1) do not affect HCV replication, although other enviroxime-like compounds can affect both enteroviral and HCV replication [109]. On the other hand, 4 anilino quinazolines were first reported to have antiviral activity against HCV, although the mechanism was not well defined. However, a recent study has associated the antiviral activity of a representative 4-anilino quinazoline (AL-9) with the inhibition of PI4KIIIα during HCV infection, which opens new therapeutic approaches [179]. Since the viral protein NS5A directly interacts with PI4KIIIα during HCV infection [125,127], modulation

Overall, these examples of drugs targeting different enzymes related to phosphoinositide metabolism support this strategy as a feasible approach for antiviral drug discovery. In this line, related phosphoinositide kinases constitute an important emerging class of drug targets

Sphingolipids constitute a major component of lipid rafts [37,38], which, as commented before, are involved in different steps of viral infection, making sphingolipids potential antiviral targets. Along this line, ebolavirus requires the activity of acid sphingomyelinase, the enzyme that converts sphingomyelin to phosphocholine and ceramide for infection, and depletion of sphingomyelin reduces its infection [206]. A dependence on sphingomyelin for HCV replication has also been documented [130]. Inhibition of serine palmitoyltransferase, the enzyme that catalyzes the first step on sphingolipid biosynthesis, using myriocin has also been assayed against HCV or hepatitis B virus, either alone or in combination with interferon [180-182]. However, a certain controversy exists regarding whether the inhibitory effect of myriocin on HCV replication is attributable to the specific inhibition of serine palmitoyltransferase, since FTY720, a compound that like myriocin is structurally similar to sphingosine but does not inhibit serine palmitoyltransferase, also inhibits HCV replication

The analysis of the functions of cellular factors in viral infections has highlighted the role of different lipid species in these infections. Viruses can use cellular lipids like bricks to build viral particles or to develop viral replication complexes, thus facilitating its multiplication. But viruses can also manipulate host cell metabolism towards the production of specific lipid species, unveiling an intimate relationship between viruses and host cell lipid

proteins could also constitute a novel antiviral strategy [122].

of this interaction also raises novel possibilities for antiviral research.

**3.4. Sphingolipids as antiviral targets** 

Miguel A. Martín-Acebes, Ángela Vázquez-Calvo, Flavia Caridi and Francisco Sobrino *Department of Virology and Microbiology, Centre for Molecular Biology "Severo Ochoa" (CBMSO) (UAM/CSIC), Cantoblanco, Madrid, Spain* 

Juan-Carlos Saiz *Department of Biotechnology, National Institute for Food Science and Technology (INIA), Madrid, Spain* 
