Antiviral agents experimental

B. S. Kwon, L. P. Gangarosa, N. H. Park, D. S. Hull, E. Fineberg, C. Wiggins, and J. M. Hill. Effect of iontophoretic and topical application of antiviral agents in treatment of experimental HSV-1 keratitis in rabbits. Invest Ophthalmol Vis Sci 18 984-988 (1979)... 

This is an antiviral agent which was accidentally discovered to be of some value in the initial treatment of Parkinson s disease. While the precise mechanism of action of this drug is uncertain, there is experimental evidence to show that it increases the release and synthesis of dopamine and inhibits its reuptake, thereby facilitating the action of the neurotransmitter in those dopaminergic terminals that are still able to function. It has been found that patients soon develop a tolerance to the beneficial effects of the drug, which has largely precluded its long-term use. 

There is at least one example in the literature (330) in which the calculated affinity difference did not agree with the experimental date [binding of an antiviral agent to human rhinovirus HRV-14 and to a mutant virus in which a valine was mutated to a leucine (Fig. 3.26)J. Here a j8-branched amino acid (Val) was converted into Leu, which lacks the isopropyl side chain adjacent to the peptide backbone besides the addition of a methyl group. 

Several compounds have been used in treating chronic viral hepatitis. Experimental and clinical studies have focused on four groups of substances (7.) antiviral agents, (2.) immunostimulants, (i.) molecular biological agents, and 4.) adjuvant medicinal remedies. The rate of spontaneous seroconversion is 8-15%lyear... 

Mycil chlorphenesin tolnafitate. mycophenolate mofetil [usan] (CellCept ) is converted in vivo to n cophenolic add, which has antimetabolite cytotoxic properties. It shows experimental activity as an ANTICANCER and ANTIVIRAL AGENT. It may be clinically useful in treating psoriasis and as an ANTU.EISHMANIAL. It shows IMMUNOSUPPRESSANT properties, and is used in the prophylaxis of acute kidney rejection, mycophenolic acid [ban, inn, usan] is usually... 

Isol. from the marine gorgonian Eunicella cavolini and Streptomyces spp. Antiviral agent shows significant activity against Herpes simplex and vaccinia viruses in cell cultures and in experimental animals. Nucleoside transporter substrate. 

In vitro, cydopentadienyl metal complexes were able to suppress the proliferation of normal or transformed tumor cells. Best activity was found for vanadocene dichloride in this respect. In vivo, numerous of the cydopentadienyl metal complexes inhibited the development of diverse experimental animal tumors (e.g., Ehrlich asdtes tumor, sarcoma 180, B16 melanoma, colon 38 cardnoma and Lewis lung cardnoma) and the growth of human cardnomas xenografted to nude mice. Espedally certain titanocene and ferricenium compoimds were cytostatically effective against human colorectal cardnomas. Moreover, titanocene complexes were shown to be antiviral agents and potent antiinflammatory compounds comparable to phenylbutazone. 

Used as experimental tools, all the nucleic acid binding drugs mentioned in Paragraph 8.1.6 have some kind of antiviral activity (proflavine, daunomycin, actinomycin-D, etc.). Other potential antiviral agents are considered here, as well as substances which for different reasons are more active against the viral than the normal cell metabolism, and interferon which is a natural means of defence of the cell against viral invasion. 

It can, therefore, be suggested as a general working hypothesis that the efficacy of 3-DZA and other AdoHcy hydrolase inhibitors and/ or AdoHcy analogs as antiviral agents relates to their ability to modulate or inhibit the reactions that lead to the synthesis of a fully methylated 5 -cap structure in viral mRNAs. Considerable experimental evidence supporting this hypothesis has been accumulated, but the critical demonstration of its validity is not yet available. 

Table 3 Antiviral activity of the preferred experimental agent, 1-152, /V-(7V-acetyl-l.-cystcinyl)-S-acetylcysteamine, in spleen MDMs infected with 10000 TCID50s of the HIV-l/Ba-L isolate at 50, 70 and 90% effective doses...

Ribavirin is an antiviral drug with efficacy for treatment of the arenaviruses and bunyaviruses. Passively administered antibody is also effective in therapy of some viral hemorrhagic fevers. The only licensed vaccine available for VHF agents is for yellow fever. Experimental vaccines exist for Junin, RVF, hantaan, and dengue viruses, but these will not be licensed in the near future. 

PeniciUic acid is a cytotoxic agent with antibacterial and antiviral effects. During repeated administration to experimental animals its hepatotoxicity and nephrotoxicity have been demonstrated. PeniciUic acid is a relatively unstable compound, which reacts readily with suUhydryl substances under opening the lactone ring (as patuhn) and a loss of toxicity. 

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