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The synthesis of novel nucleotide analogues on the basis of ethylphosphonic acid was described. A rigid structural element, an amide or a double bond, was characteristics of the compounds synthesized. The antiviral and cytotoxic activities of these compounds were studied in cell cultures.
Abstract The α-and β-D-Xylofuranosyl and -lyxofuranosyl analogues of the five naturally occurring nucleic acid bases have been the subject of a systematic synthesis and examination of some of their biological properties, i.e. antiviral, antimetabolic and cytostatic activities.
A large variety of compounds have been reported to inhibit the replication of human immunodeficiency virus (HIV). The compounds that have been most intensively pursued for the treatment of HIV infection belong to three classes: nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Within each of these classes, a number of compounds have been identified that inhibit HIV replication at nanomolar concentrations which are 10(4)- to 10(5)-fold lower than the cytotoxic concentrations. Yet, the potential usefulness of these compounds seems to be compromised by the rapid emergence of virus drug resistance. Here, we describe a strategy that, at least in cell culture, prevents the development of resistance. This strategy is based on the use, from the beginning, of sufficiently high drug concentrations. When added at such concentrations, that for some of the NNRTIs did not have to be higher than 10-100 times their 50% effective concentration (EC50), these compounds completely suppressed ("knocked out") HIV-1 replication in cell culture, and thus prevented drug-resistant virus strains from emerging. This "knock out" effect could be achieved for longer times and at lower drug concentrations when the compounds were combined (i.e. NNRTIs with one another or with NRTIs) than when used individually. Thus, when used at the appropriate doses, as such or in combination, NNRTIs proved able to completely clear ("cure") HIV-1-infected cell cultures from the virus.
Cidofovir is a nucleotide analog marketed for the treatment of human cytomegalovirus infections in immunocompromised patients. An increasing number of reports have appeared on the use of cidofovir for the treatment of other severe DNA virus infections in immunocompromised patients. The activity of cidofovir against herpes simplex viruses resistant to classic (acyclovir and/or foscavir) therapy has been widely documented. Cidofovir has also been used for the treatment of other herpesvirus infections, such as drug-resistant varicella-zoster virus, and Epstein-Barr virus-induced proliferative diseases. For papillomavirus infections, cidofovir represents a valuable alternative to the conventional therapies, which are mostly based on surgery, as in the treatment of laryngeal papillomatosis. The role of cidofovir in the treatment of polyomavirus infections is more controversial, but here too, cidofovir represents, to date, the only available efficacious therapeutic modality. Cidofovir has demonstrated activity against all poxviruses and represents a unique therapeutic modality for use against these viruses, particularly in the immunosuppressed host, should this prove necessary (eg, in a bioterrorism scenario).
Non-linear process plans are process plans which comprise different manufacturing alternatives Such non-linear process plans increase the flexibility of scheduling activities and allow to remedy quickly to disturbances in the workshop They are represented by Petn nets The automatic generation of a non-linear process plan is realised m different steps: - the feature based workpiece description is transformed into a non-linear sequence of operation steps: - the resources capable to manufacture : he specified operation steps, are determined. - the non-linear sequence is converted into a non-linear process plan which is directly usable for scheduling The developed CAPP system has been rested ‘or hydraulic components
A marked virus-inhibiting potency is obtained in the serum after intraperitoneal injection of polyacrylic acid (PAA) and polymethacrylic acid (PMAA) in mice. Much higher antiviral levels were reached than for other related polymers including dextran sulfate, heparin, polyvinyl sulfate, pyran copolymer, polystyrene sulfonate, and macrodex. The broad antiviral action of PAA and PMAA was attributed both to a direct interference with the virus-cell interaction and the viral ribonucleic acid metabolism and to the formation of an interferon-like factor. Both polyanions differed in interferon-inducing ability: highest serum interferon titer was obtained 18 hr after the intraperitoneal injection of PAA. The mechanism of interferon production by PAA and PMAA is discussed. As described previously for Sindbis virus and endotoxin, the animals also became hyporeactive after injection of PAA.
