Antiviral Treatment: From Concept to Reality

Abstract

The initial development of antiviral compounds was slow, with the first clinical antiviral agent not available until the 1960s. Early development was hindered by the lack of understanding of virus life-cycles and the absence of an assay system for antiviral activity. The appearance of the first assay system, the fertilized egg yolk sac, led to the identification of methisazone. This was the first antiviral agent to be used clinically. The improvement in antiviral assay systems, and the start of directed research programmes led to the development of the first antiherpes agents idoxuridine, trifluorothymidine (TFT) and vidarabine. However, all of these agents were associated with significant adverse effects. Antiherpes therapy took a major step forward with the development of the acyclic nucleoside analogue, aciclovir. Aciclovir is much more potent than previous antiherpesvirus agents. Its mode of action results in selectivity for herpesvirus-infected cells, thus significantly reducing the side-effects seen with earlier agents. Because of this, it became the standard therapy for herpes simplex virus type 1 (HSV-1), HSV-2 and varicella zoster virus infections. However, the bioavailability of oral aciclovir is poor, requiring high and frequent doses. This led to the search for better absorbed agents and to the development of two prodrugs, famciclovir and valaciclovir. Both famciclovir and valaciclovir offer much improved bioavailability of the nucleosides penciclovir and aciclovir, compared with aciclovir. Once in the body the conversion of valaciclovir to aciclovir means that the two agents have similar pharmacokinetic properties. Similarly, famciclovir is converted to penciclovir in the body. Penciclovir, when phosphorylated in virus-infected cells, persists within the cell for a much longer period than aciclovir triphosphate. Over the last 10 years we have seen an acceleration in the development of antiviral agents and some major advances in antiviral therapy. Many challenges, however, still lie ahead.

Herpes zoster: modern clinical features and the principles of therapeutic management

“…Однако следует отметить, что валацикловир по сравнению ацикловиром имеет в 3-5 раз более высокую био-доступность. Также существенным преимуществом валацикловира является пролонгированное время действия препарата внутри инфицированной клет-ки (10-20 ч), которое не зависит от его концентра-ции в крови и позволяет сократить кратность прие-ма до 2 раз в сутки [5,7].…”

Quantum Chemical Calculations for some Isatin Thiosemicarbazones

“…Derivatives of isatin are reported to be present in mammalian tissues and body fluids (Casas et al, 1996;Agrawal & Sartorelli, 1978;Casas et al, 1994;Medvedev et al, 1998;Boon, 1997;Pandeya & Dimmock, 1993;Rodríguez-Argüelles et al, 1999;Casas et al, 2000) and possess antibacterial (Daisley & Shah, 1984), antifungal (Piscopo et al, 1987), and anti-HIV (Pandeya et al, 1998(Pandeya et al, , 1999 activities. N-methylisatin--4', 4' -diethylthiosemicarbazone were also reported to have activity against the viruses such as cytomegalo and moloney leukemia viruses (Sherman et al, 1980;Ronen et al, 1987).…”

Synthesis, characterization and biocidal activity of some transition metal(II) complexes with isatin salicylaldehyde acyldihydrazones

“…Over the recent years, more attention has been focused on the coordination chemistry and biological properties of different metal complexes of isatin-thio-semicabazones 4,5 , bis-(thio-semicarbazones 6 ), semicarbazones 7 and hydrazones 8,9 in order to establish a possible relationship between chemical structure and biological activity. Schiff and Mannich bases of isatin were reported to possess antibacterial 10 , antifungal 11 , antiviral 12 , anti-HIV 13 , anti protozoal 14 , antiviral 15 and anticancer 16 . Within the context of enzyme inhibitors, isatin derivatives have found recent applications in the inhibition of cysteine and serine proteases 17,18 .…”