Milestone articles


1. De Clercq, E. & De Somer, P.

    Antiviral activity of polyribocytidylic acid in cells primed with polyriboinosinic acid.

    Science, 173: 260-262 (1971).


2. De Clercq, E.

    Suramin : a potent inhibitor of the reverse transcriptase of RNA tumor viruses.

    Cancer Letters, 8: 9-22 (1979).


3. De Clercq, E., Descamps, J., De Somer, P., Barr, P.J., Jones, A.S. & Walker, R.T.

    E-5-(2-Bromovinyl)-2'-deoxyuridine : a potent and selective an¬tiherpes agent.

    Proc. Nat. Acad. Sci. USA, 76: 2947-2951 (1979).


4. Derynck, R., Content, J., De Clercq, E., Volckaert, G., Tavernier, J., Devos, R. & Fiers, W.

    Isolation and structure of a human fibroblast interferon gene.

    Nature, 285: 542-547 (1980).


5. Derynck, R., Remaut, E., Saman, E., Stanssens, P., De Clercq, E., Content, J. & Fiers, W.

    Expression of the human fibroblast interferon gene in Escherichia coli.

    Nature, 287: 193-197 (1980).


6. De Clercq, E., Degreef, H., Wildiers, J., De Jonge, G., Drochmans, A., Descamps, J. & De Somer, P.

    Oral (E)-5-(2-bromovinyl)-2'-deoxyuridine in severe herpes zoster infections.

    Brit. Med. J., 281: 1178 (1980).


7. Content, J., De Wit, .L, Pierard, D., Derynck, R., De Clercq, E. & Fiers, W.

    Secretory proteins induced in human fibroblasts under conditions used for the production of interferon beta.

    Proc. Natl. Acad. Sci. USA, 79: 2768-2772 (1982).


8. Colla, L., De Clercq, E., Busson, R. & Vanderhaeghe, H.

    Synthesis and antiviral activity of water-soluble esters of acyclovir [9-(2-hy-droxyethoxymethyl)guanine].

    J. Med. Chem., 26: 602-604 (1983).


9.  De Clercq, E., Holý, A., Rosenberg, I., Sakuma, T., Balzarini, J. & Maudgal, P.C.

     A novel selective broad-spectrum anti-DNA virus agent.

     Nature, 323: 464-467 (1986).


10. De Clercq, E., Sakuma, T., Baba, M., Pauwels, R., Balzarini, J., Rosenberg, I. & Holý, A.

      Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines.

      Antiviral Res., 8: 261-272 (1987).


11. Baba, M., Pauwels, R., Herdewijn, P., De Clercq, E., Desmyter, J. & Vandeputte, M.

      Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of
      human immunodeficiency virus replication in vitro.

      Biochem. Biophys. Res. Commun., 142: 128-134 (1987).


12. Baba, M., Tanaka, H., De Clercq, E., Pauwels, R., Balzarini, J., Schols, D., Nakashima, H., Perno, C.-F., Walker, R.T. & Miyasaka, T.

      Highly specific inhibition of human immunodeficiency virus type 1 by a novel 6-substituted acyclouridine derivative.

      Biochem. Biophys. Res. Commun., 165: 1375-1381 (1989).


13. Miyasaka, T., Tanaka, H., Baba, M., Hayakawa, H., Walker, R.T., Balzarini, J. & De Clercq, E.

      A novel lead for specific anti-HIV-1 agents: 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.

      J. Med. Chem., 32: 2507-2509 (1989).


14. Pauwels, R., Andries, K., Desmyter, J., Schols, D., Kukla, M.J., Breslin, H.J., Raey-maeckers, A., Van Gelder, J., Woestenborghs, R.,
      Heykants, J., Schellekens, K., Janssen, M.A.C., De Clercq E. & Janssen, P.A.J.

      Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives.

      Nature, 343: 470-474 (1990).


15. De Clercq, E., Yamamoto, N., Pauwels, R., Baba, M., Schols, D., Nakashima, H., Balzarini, J., Debyser, Z., Murrer, B.A., Schwartz, D.,
      Thornton, D., Bridger, G., Fricker, S., Henson, G., Abrams, M. & Picker, D.

      Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting
      with a viral uncoating event.

      Proc. Natl. Acad. Sci. USA, 89: 5286-5290 (1992).


16. Balzarini, J., Holý, A., Jindrich, J., Naesens, L., Snoeck, R., Schols, D. & De Clercq, E.

      Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enan¬tiomers of acyclic nucleoside phosphonates: potent and
      selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine.

      Antimicrob. Agents Chemother., 37: 332-338 (1993).


17. De Clercq, E., Yamamoto, N., Pauwels, R., Balzarini, J., Witvrouw, M., De Vreese, K., Debyser, Z., Rosenwirth, B., Peichl, P., Datema, R.,
      Thornton, D., Skerlj, R., Gaul, F., Padmanabhan, S., Bridger, G., Henson, G. & Abrams, M.

      Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100.

      Antimicrob. Agents Chemother., 38: 668-674 (1994).


18. Schols, D., Esté, J.A., Henson, G. & De Clercq, E.

      Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4.

      Antiviral Res., 35: 147-156 (1997).


19. Schols, D., Struyf, S., Van Damme, J., Esté, J.A., Henson, G. & De Clercq, E.

      Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4.

      J. Exp. Med., 186: 1383-1388 (1997).


20. Donzella, G.A., Schols, D., Lin, S.W., Esté, J.A., Nagashima, K.A., Maddon, P.J., Allaway, G.P., Sakmar, T.P., Henson, G., De Clercq,
      E. & Moore, J.P.

      AMD3100, a small-molecule inhibitor of HIV-1 entry via the CXCR4 co-receptor

      Nat. Med., 4: 72-77 (1998).


21. De Clercq, E.

      Strategies in the design of antiviral drugs.

      Nat. Rev. Drug Discov., 1: 13-25 (2002).


22. De Clercq, E.

      The bicyclam AMD3100 story.

      Nat. Rev. Drug Discov., 2: 581-587 (2003).


23. De Clercq, E.

      Antivirals and antiviral strategies.

      Nat. Rev. Microbiol., 2: 704-720 (2004).


24. De Clercq, E. & Holý, A.

      Acyclic nucleoside phosphonates: a key class of antiviral drugs.

      Nat. Rev. Drug Discov., 4: 928-940 (2005).


25. De Clercq, E.

      Antiviral agents active against influenza A viruses.

      Nat. Rev. Drug Discov., 5: 1015-1025 (2006).


26. De Clercq, E.

      The design of drugs for HIV and HCV.

      Nat. Rev. Drug Discov., 6: 1001-1018 (2007).


27. De Clercq, E.

      Pre-exposure chemoprophylaxis of HIV infection: Quo vadis ?

      Biochem. Pharmacol., 83: 567-573 (2012).


28. De Clercq, E.

      Where rilpivirine meets with tenofovir, the start of a new anti-HIV drug combination era.

      Biochem. Pharmacol., 84: 241-248 (2012).


29. De Clercq, E.

      Antivirals: past, present and future.

      Biochem. Pharmacol., 85: 727-744 (2013).


30. De Clercq, E.

      Current race in the development of DAAs (direct-acting antivirals) against HCV.

      Biochem. Pharmacol., 89: 441-452 (2014).


31. De Clercq, E.

      Ebola virus (EBOV) infection: Therapeutic strategies.

      Biochem. Pharmacol., 93: 1-10 (2015).



Why milestones?


  • Ref. 2. Suramin later emerged as the first drug found active against HIV in vitro and in vivo.

  • Ref. 4 and 5. Interferon-β has been used for treatment of multiple sclerosis.

  • Ref. 8. The valine ester of acyclovir (valaciclovir) would succeed acyclovir as antiviral drug.

  • Ref. 9, 10 and 24. The basis of the discovery of the acyclic nucleoside phosphonates (including adefovir and cidofovir).

  • Ref. 11. Discovery of stavudine (d4T), one of the most successful anti-HIV drugs.

  • Ref. 12, 13 and 14. Discovery of the first NNRTIs (HEPT, TIBO) (non-nucleoside reverse transcriptase inhibitors) for treatment of HIV.

  • Ref. 15 and 17. Discovery of the bicyclam AMD3100 as anti-HIV agent; would later be identified as CXCR4 antagonist (ref. 18, 19 and 20), now commercialized as stem cell mobilizer (ref. 22).

  • Ref. 16. Discovery of (R)-PMPA (tenofovir).

  • Ref. 27. Prevention of HIV infections.

  • Ref. 28. Combination for treatment of HIV infections.



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Rega Institute for Medical Research


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Lineup of key pharmaceuticals

Products resulting from the Holý-De Clercq collaboration and commercialized by Gilead (photo courtesy Gilead Sciences, Inc.)