Curriculum vitae

Enzo Tramontano holds a degree from the University of Cagliari (1990), he was Visiting Research Scientist at the Dept. of Pharmacology at Yale University Medical School (CT, USA, 1990-1992 and 1996-1998). Since 1998 he has worked at the Departments of Experimental Biology (1998-2003), Biomedical Sciences and Technologies (2003-2007), Applied Sciences in Biosystems (2007-2010) and Life and Environmental Sciences (2011-2013) at the University of Cagliari. He is currently Vice-Director of the Department of Life and Environmental Sciences of the University of Cagliari and Coordinator of the PhD program Life, Environmental and Drug Sciences. He is member of the European Society of Virology, the International Society for Antiviral Research, the American Society of Microbiology, the Italian Society of Virology and the Italian Society of General Microbiology and Microbial Biotechnologies.

Lines of research

A first line of research is focused on the understanding and characterization of enzymatic reactions performed by proteins which are validated target for drug development. This approach is pursued by expressing and purifying recombinant proteins which are subsequently functionally characterized in biochemical assays. The research is then focused on the discovery, design and development of new drug leads. Mechanism of action and structure-activity relationship studies, including elucidation of target enzyme/protein-drug interaction, and drug resistance characterization are performed.

1. More specifically this line of research focused to two projects:
   Identification of HIV-1 RT associated RNase H activity inhibitors.
   One of the most promising new viral targets that can be used for the development of new anti-HIV drugs is the RT-associated RNase H function. This function is involved in the selective degradation of the RNA of the double stranded hybrid RNA-DNA produced by the retrotranscription process and is essential for viral replication. Therefore, HIV RNase H is a validated target for drug development.
2. Characterization of Ebola Virus VP35 function and identification of inhibitors. VP35 is one of the nine viral proteins encoded by Ebola viruses genome. It consists of 340 aminoacid residues with a molecular weight of about 36 kDa. VP35 is a multifunctional protein: it is an essential component of the viral RNA polymerase complex and is involved in the nucleocapsid assembly. Furthermore, VP35 plays a key role in the EBOV interference with the host cell innate immune responses. VP35 structure and functionalities indicate that it is a double strand RNA binding protein and that it interacts with cellular factors involved in the type I interferon-mediated antiviral response.

A second line of research is focused on the identification and characterization of retroviral sequences that are stably integrated into the human genomes. These sequences are generally referred to as human endogenous retrovirus (HERV). During evolution HERVs sequences have hoarded abundant mutations, both deletions and insertions, duplications and recombinations that have caused loss of virulence, contributing to the actual HERVs composition. They were classified based on their nucleotide and amino acid similarities to exogenous retroviruses in three classes (I-III). Given their high presence in the whole human genome, HERVs are deeply investigated to clarify their potential role in physiological and pathological contexts, with particular attention to the possible correlation with the development of malignant tumors, autoimmune diseases and other disorders. The current project is based on both bioinformatics and traditional laboratory approaches to identify and characterize HERVs sequences in the human genome and link them to possible functional roles.

Website

http://people.unica.it/enzotramontano/lang/it

Publications from 2009 to 2014

1. 1. Cannas V, Daino GL, Corona A, Esposito F and Tramontano E. A luciferase reporter gene assay to measure Ebola Virus viral protein 35–associated inhibition of double-stranded RNA–stimulated, retinoic acid–inducible gene 1–mediated induction of interferon β J. Infect. Disease 2015 in press
2. Babkov DA, Chizhov AO, Khandazhinskaya AL, Corona A, Esposito F, Tramontano E, Seley-Radtke KL, Novikov MS An efficient route to novel uracil based drug-like molecules. Synthesis 47: 1413-1422 (2015).
3. Xu L, Grandi N, Del Vecchio C, Mandas D, Corona A, Piano D, Esposito F, Parolin C, Tramontano E. From the traditional Chinese medicine plant Schisandra chinensis new scaffolds effective on HIV-1 reverse transcriptase resistant to non-nucleoside inhibitors. J Microbiol. 53: 288-293 (2015)
4. Meleddu R, Distinto S, Corona A, Bianco G, Cannas V, Esposito F, Artese A, Alcaro S, Matyus P, Bogdan D, Cottiglia F, Tramontano E, Maccioni E. 3Z)-3-(2-[4-(aryl)-1,3-thiazol-2-yl]hydrazin-1-ylidene)-2,3-dihydro-1H-indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase. Eur J Med Chem. 2015 93C: 452-460 (2015) doi: 10.1016/j.ejmech.2015.02.032.
5. Cuzzucoli Crucitti G, Métifiot M, Pescatori L, Messore A, Madia VN, Pupo G, Saccoliti F, Scipione L, Tortorella S, Esposito F, Corona A, Cadeddu M, Marchand C, Pommier Y, Tramontano E, Costi R, Di Santo R. Structure-Activity Relationship of Pyrrolyl Diketo Acid Derivatives as Dual Inhibitors of HIV-1 Integrase and Reverse Transcriptase Ribonuclease H Domain. J Med Chem. 58: 1915-28 (2015) doi: 10.1021/jm501799k.
6. Corona A, Di Leva FS, Thierry S, Pescatori L, Cuzzucoli Crucitti G, Subra F, Delelis O, Esposito F, Rigogliuso G, Costi R, Cosconati S, Novellino E, Di Santo R, Tramontano E. Identification of highly conserved residues involved in the inhibition of the HIV-1 ribonuclease H function by diketoacid derivatives. Antimicrob Agents Chemother. 58: 6101-6110 (2014).
7. Carcelli M, Rogolino D, Sechi M, Rispoli G, Fisicaro E, Compari C, Grandi N, Corona A, Tramontano E, Pannecouque C, Naesens L. Antiretroviral activity of metal-chelating HIV-1 integrase inhibitors. Eur J Med Chem. 83: 594-600 (2014).
8. Corona A., Esposito F., Tramontano E. Can the ever-promising target HIV reverse transcriptase-associated RNase H become a success story for drug development? Future Virology 9: 445-448 (2014).
9. Meleddu R, Cannas V.,  Distinto S, Sarais G.,  Del Vecchio C., Esposito F., Bianco G., Corona A., Cottiglia F., Alcaro F., Parolin C., Artese A., Scalise D.,  Fresta M., Arridu A., Ortuso F., Maccioni E. and Tramontano E.  Design, Synthesis and Biological Evaluation of New 1,3-Diarylpropenones as Dual Inhibitors of HIV-1 RT (2014) Chem. Med. Chem. 9: 1869-79 (2014).
10. Corona A, Schneider A, Schweimer K, Rösch P, Wöhrl BM, Tramontano E. Inhibition of foamy virus reverse transcriptase by human immunodeficiency virus type 1 ribonuclease H inhibitors. (2014) Antim. Agents Chemother. 58, 4086-4093 (2014).
11. Farci D., Bowler M.W., Kirkpatrick J., McSweeney S., Tramontano E., Piano D. New features of the cell wall of the radio-resistant bacterium Deinococcus radiodurans. Biochim Biophys Acta. 1838: 1978-1984 (2014).
12. Esposito F. and Tramontano E. Past and future. Current drugs targeting HIV-1 integrase and reverse transcriptase-associated ribonuclease H activity: single and dual active site inhibitors. Antiv. Chem. Chemother. 23, 129-144 (2014).
13. Corona A., Masaoka T., Tocco G., Tramontano E., Le Grice SFJ. Active site and allosteric inhibitors of the ribonuclease H activity of HIV reverse transcriptase. Future Med. Chem. 5, 2127-2139 (2013).
14. Zinzula L., Tramontano E. Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I-like receptors: hide, mask, hit. Antiviral Res. 100, 615-635 (2013).
15. Costi R., Métifiot M., Esposito F., Cuzzucoli Crucitti G., Pescatori L., Messore A., Scipione L., Tortorella S., Zinzula L., Marchand C., Pommier Y., Tramontano E., Di Santo R. 6-(1-Benzyl-1H-pyrrol-2-yl)-2,4-dioxo-5-hexenoic Acids as Dual Inhibitors of recombinant HIV-1 Integrase and Ribonuclease H, Synthesized by a Parallel Synthesis Approach. J. Med. Chem. 56, 8588−859 (2013).
16. Tocco G., Begala M., Esposito F., Caboni P., Cannas V., Tramontano E. ZnO-mediated regioselective C-arylsulfonylation of indoles: a facile solvent-free synthesis of 2- and 3-sulfonylindoles and preliminary evaluation of their activity against drug-resistant mutant HIV-1 reverse transcriptases (RTs). Tetrahedron Lett 54, 6237-6241 (2013).
17. Esposito F., Sanna C., Del Vecchio C., Cannas V., Venditti A., Corona A., Bianco A., Serrilli A.M., Guarcini L., Parolin C., Ballero M. and Tramontano E. Hypericum hircinum L. components as new single molecule inhibitors of both HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities Pathog. Dis. 68, 116-124 (2013).
18. Distinto S., Maccioni E., Meleddu R., Corona A., Alcaro S. and Tramontano E. Molecular Aspects of the RT/Drug Interactions. Perspective of Dual Inhibitors. Curr. Pharm. Design 19, 1850-1859 (2013).
19. Esposito F., Corona A., Zinzula L., Kharlamova T., Tramontano E. New anthraquinone derivatives as inhibitors of the HIV-1 reverse transcriptase-associated Ribonuclease H function. Chemotherapy. 25, 299-307 (2012).
20. Esposito F., Corona A., Tramontano E. HIV-1 reverse transcriptase still remains a new drug target: structure, function, classical inhibitors, and new inhibitors with innovative mechanisms of actions. Molecular Biology International, Vol. 2012, Article ID 586401, doi:10.1155/2012/586401.
21. Suchaud V., Bailly F., Lion C., Tramontano E., Esposito F., Corona A., Christ F., Debyser Z., Cotelle P. Development of a series of 3-hydroxyquinolin-2(1H)-ones as selective inhibitors of HIV-1 reverse transcriptase associated RNase H activity. Bioorg. Med. Chem. Lett. 22, 3988-3992 (2012).
22. Distinto S., Esposito F., Kirchmair J., Cardia MC., Gaspari M., Maccioni E., Alcaro S., Markt P., Wolber G., Zinzula L., Tramontano E. Identification of HIV-1 reverse transcriptase dual inhibitors by a combined shape-, 2D-fingerprint- and pharmacophore-based virtual screening approach Eur. J. Med. Chem. 50, 1-14 (2012).
23. Zinzula L., Esposito F., Pala D. and Tramontano E. dsRNA binding characterization of full length recombinant wild type and mutants Zaire ebolavirus VP35. Antiv. Res. 93, 354-363 (2012).
24. Sun Y., Luo H., Li Y., Sun C., Song J., Niu Y., Zhu Y., Dong L., Lv A., Tramontano E. and Chen S. Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes Involved in camptothecin biosynthesis and transport BMC Genomics 12, 533 (2011).
25. Tramontano E., Kharlamova T., Zinzula L. and Esposito F. Effects of new quinizarin derivatives on both HCV NS5B RNA polymerase and HIV-1 reverse transcriptase associated ribonuclease H activities J. Chemother. 23, 273-276 (2011).
26. Esposito F., Zinzula L., Maxia A., Tramontano E. and Sanna C. Inhibition of HIV-1 reverse transcriptase associated activities by the hydroalcoholic extract of the Casimiroa edulis seeds Nat. Prod. Res 25, 1067-73, (2011).
27. Esposito F, Kharlamova T, Distinto S, Zinzula L., Cheng Y-C., Dutschman G., Floris G., Markt P., Corona A. and Tramontano E. Alizarine derivatives as new dual inhibitors of the HIV-1 reverse transcriptase(RT)-associated DNA polymerase and Ribonuclease H (RNase H) activities effective also on the RNase H activity of non-nucleoside resistant RTs FEBS J. 278, 1444-1457, (2011).
28. Tramontano E. and Di Santo R. HIV-1 RT-associated RNase H function inhibitors: recent advances in drug development Curr. Med. Chem. 17, 2837-2853, (2010).
29. Kharlamova T., Esposito F., Zinzula L., Floris G., Cheng Y-C., Dutschman G.E and Tramontano E. Inhibition of HIV-1 Ribonuclease H activity by novel frangula-emodine derivatives Med. Chem. 5, 398-410, (2009).
30. Esposito F., Fanti V., Marzeddu R., Randaccio P., Tramontano E., Zinzula L. Validation of a Computed Radiography device to monitor the HIV-1 RNase H activity. Nucl. Instr. Meth. Phys. Res. 607, 226-228 (2009).
31. Bicchi C., Rubiolo P., Ballero M., Sanna C., Matteodo M., Esposito F., Zinzula L. and Tramontano E. HIV-1 inhibiting activity of the essential oil of Ridolfia segetum and Oenanthe crocata Planta Medica 75: 1-5 (2009).
32. Zinzula L., Esposito F., Mühlberger E., Trunschke M., Conrad D., Piano D. and Tramontano E. Purification and functional characterization of the full length recombinant Ebola virus VP35 protein expressed in E. coli Prot. Expr. Purif. 66: 113-119, (2009).
33. Nurchi V.M., Crisponi G., Pivetta T., Tramontano E., Cesare Marincola F. and Lachowicz J.I. Interaction between aspergillic acid and iron(III): A potentiometric, UV–Vis, 1H NMR and quantum chemical study Polyhedron 28: 763-768, (2009).