Curious discoveries in antiviral drug development: the role of serendipity

Medicinal Research Reviews
Erik De Clercq

Abstract

Antiviral drug development has often followed a curious meandrous route, guided by serendipity rather than rationality. This will be illustrated by ten examples. The polyanionic compounds (i) polyethylene alanine (PEA) and (ii) suramin were designed as an antiviral agent (PEA) or known as an antitrypanosomal agent (suramin), before they emerged as, respectively, a depilatory agent, or reverse transcriptase inhibitor. The 2',3'-dideoxynucleosides (ddNs analogues) (iii) have been (and are still) used in the "Sanger" DNA sequencing technique, although they are now commercialized as nucleoside reverse transcriptase inhibitors (NRTIs) in the treatment of HIV infections. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (iv) was discovered as a selective anti-herpes simplex virus compound and is now primarily used for the treatment of varicella-zoster virus infections. The prototype of the acyclic nucleoside phosphonates (ANPs), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (v) was never commercialized, although it gave rise to several marketed products (cidofovir, adefovir, and tenofovir). 1-[2-(Hydroxyethoxy)methyl]-6-(phenylthio)thymine (vi) and TIBO (tetrahydroimidazo[4,5,1-jk][1,4-benzodiazepin-2(1H)]-one and -thione) (vii)...Continue Reading

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Citations

Sep 16, 2015·Expert Opinion on Drug Discovery·Boshi HuangXinyong Liu
Sep 19, 2015·Future Medicinal Chemistry·Anke WagnerJens Kurreck
Jun 27, 2015·Antiviral Research·Irina C AlbulescuMartijn J van Hemert
Apr 25, 2014·BMC Research Notes·Trygve Nissen, Rolf Wynn
Jul 20, 2012·Trends in Pharmacological Sciences·Mark A GeyerRené S Kahn
Jun 5, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·M PrasathR Arun Balaji
Apr 18, 2019·Beilstein Journal of Organic Chemistry·David J JonesTimothy P O'Sullivan
Oct 6, 2017·The Journal of Antimicrobial Chemotherapy·Kuan-Chieh ChingChristina L L Chai
Feb 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guangdi LiLi Tan
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Pedro VizánSergi Aranda

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