Molecules that block virus entry by interfering with the actions of viral fusion proteins are of primary concern in the search for antiviral drugs. We present here the synthesis and antiviral activities of lipid–oligonucleotide conjugates (Lipoquads) forming a highly stable tetramolecular parallel G-quadruplex. We show that these molecules block HIV-1 and HIV-2 entry with submicromolar activities, demonstrating the great advantage of targeting both viral envelope glycoprotein and lipid rafts—a key platform in virus entry. Because the behavior of envelope proteins is similar in several other enveloped viruses, Lipoquads may have broader activities against enveloped viruses.
Supplementary Materials
The following are available online at www.mdpi.com/2504-3900/1/6/670/s: Poster S: Lipid-Oligonucleotide Conjugates Forming G-Quadruplex (Lipoquads) as Potent Inhibitors of HIV Entry.
Acknowledgments
Financial support by the Red de Investigación en Sida del Fondo de Investigación Sanitaria de la Seguridad Social (FIS) and the Spanish Ministry of Economy (MICINN) and Competitiveness and FEDER (Grants no. BFU2013-44629-R, CTQ2014-52588-R and SAF2013-46077-R). CIBER-BBN is an initiative funded by the VI National R+D+i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. SL acknowledges funding by the Marie-Curie IEF fellowship (FP7-Grant Agreement 237738) and dedicates this work to the memory of Ian Fraser Kilmister.
Author Contributions
S.L., S.G., G.M., and R.E. designed, synthesized and purified the lipid-oligonucleotide conjugates as well as performed the assembly of the lipoquads. C.A.-F., S.S.-P., E.F., J.M., and A.M. characterized the antiviral properties of lipoquads.
Conflicts of Interest
The authors declare no conflict of interest
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