The discovery of antiviral agents: Ten different compounds, ten different stories

Abstract

This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry.

Another ten stories in antiviral drug discovery (part C): “Old” and “new” antivirals, strategies, and perspectives

“…1 However, unwittingly, the story of acyclovir is going back to the avant-garde year 1964 when Privat de Garilhe and de Rudder 111 first described the antiviral activity of adenine arabinoside (vidarabine, ara-A), an observation that was further followed up by Schabel 112 Ara-A was the first of the nucleoside analogues antivirals to be sufficiently nontoxic to be given systemically and Whitley et al 113 proved beyond doubt the clinical value of this compound, demonstrating for the first time that, providing treatment was commenced early in the disease, it was possible to curtail varicella-zoster (VZV) infections, i.e. herpes zoster in the immunosuppressed.…”

“…5), 102 the best known of this series being BVDU that has been approved and is used in most countries (except for the USA and the UK) for the treatment, upon oral administration (125 mg per day), of herpes zoster. 1 However, it should not be ignored that BVDU is also highly active against HSV-1 (but not HSV-2). 103 It has been used off label for the topical treatment of herpes labialis (cold sores) and herpetic keratitis, and for the (topical) treatment of HSV-1 keratitis BVDU has proven more efficacious than IDU and TFT.…”

“…1 I then realized that I had not covered a few important items, which should also be addressed, thus leading to a second series of stories, now in press in Medicinal Research Reviews: ''Antiviral drug discovery: ten more compounds, and ten more stories (part B).'' 2 Even before finishing this second series of stories, I felt there were yet other important stories to be told, thus prompting me to write on yet a third series of stories that were not covered at previous occasions.…”

Yet another ten stories on antiviral drug discovery (part D): Paradigms, paradoxes, and paraductions

“…This review article corresponds to the fourth paper in the series of stories on antiviral drug discovery (part D), and continues the narrative style applied for the previous parts A, B, and C on antiviral drug discovery [1][2][3] (part A was as such not labeled part A, as I could not predict at the time these stories would be followed up). To streamline the present ten stories (part D) I will label them for clarity (D1 through D10), in the context of A1 through A10, B1 through B10, and C1 through C10 for the previous stories.…”

Voltammetric Determination of Azidothymidine Using Silver Solid Amalgam Electrodes

“…Among them, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine; Fig. 1) was the first compound to be officially approved, in 1987, and marketed (as Retrovir) for the treatment of AIDS, within 2 years after its in vitro activity against the infectivity and cytopathicity of HIV in cell culture had been demonstrated [1]. It is still widely used for antiretroviral (ARV) therapy, either alone or in combination with other ARV agents [2,3].…”