Inhibition of reverse transcriptase

Phenylpyrido[l,2-3][l,2,4]triazinium salt 151 was investigated for its ability to intercalate DNA and for inhibition of reverse transcriptase. It showed moderate binding and inhibitory activity <2001AP269>. 

Trophoblastin, therefore, has been named interferon-tau (IFN-x), and is classified as a type I interferon. There are at least three or four functional IFN-x genes in sheep and cattle. The molecule displays a molecular mass of 19 kDa and an isoelectric point of 5.5-5.7, in common with other type I interferons. Interestingly, the molecule can also promote inhibition of reverse transcriptase activity in cells infected with the HIV virus. 

Up to this point, GIPF expressions have been formulated for only one type of biological activity - the inhibition of reverse transcriptase (RT), the enzyme that promotes the reverse transcription of genomic RNA into double-stranded DNA, a key step in the replication of the human immunodeficiency virus, HIV [82, 87]. Analytical representations were obtained for the anti-HIV potencies of three families of RT inhibitors the correlation coefficients are between 0.930 and 0.952. We are currently investigating the effects of applying the GIPF approach to certain portions of the molecules rather than their entireties. This might reveal the source of the activity, or alternatively, indicate it to be delocalized. 

Sethi, M. L. 1979. Inhibition of reverse-transcriptase activity by benzophenantridine alkaloids. Journal of Natural Products, 42 187-196. 

A practical synthesis of furopyridine (49), a fragment of a HIV-protease inhibitor, was accomplished starting with 6-hydroxynicotinic acid <95TL(36)4571>. Nevirapine (50), and its derivatives, have received much attention because of their inhibition of reverse transcriptase in HIV-type 1 <95JMC(38)4830> <95JMC(38)4839>. (50) has been synthesized using a directed metallation approach <95JOC(60)1875> <95H(41)753>. 

Inhibition of reverse transcriptase, alanine and aspartate aminotransferases 259,401 Inhibition of reverse transcriptase 401... 

Fagaronine Inhibition of reverse transcriptase of oncoma virus — 143... 

Lamivudine This is a cytosine(cytidine)-nucleoside analogue. Its effect is based on the inhibition of reverse transcriptase in HIV and of DNA polymerase in HBV The daily oral dosage is 1 (-3) x 100 mg/day. After discontinuation of lamivudine, the previous findings recur here, too, efficacy only exists with continued therapy. A combination with famciclovir seems promising. Its clinical application is mainly in combination with IFN. Long-term monotherapy over several years may be necessary. (48,54) (s. p. 704)... 

Table 5. Inhibition of reverse-transcriptase activity of FL-virions by distamycin derivatives in the absence of exogenous template. Virions containing Triton were preincubated at room temp, for 25 min with 50 jUg/ml of pancreatic RNase Chandra et al.6 ...

Table 11. Inhibition of reverse-transcriptase activity of FL-virions by distamycin derivatives in the absence of exogenous template...

Table 16. Inhibition of reverse-transcriptase activity of RNA tumor viruses by daunomycin derivatives. Figures in brackets are percentages...

Munson et al.41) have recently shown that DEAE-F is effective in inhibiting the established Friend viral leukemia. They believe that interferon induction may not be responsible for the antitumor activity of this compound. This suggests that the virus-associated enzymatic activities, DNA polymerases, may be sensitive towards the action of DEAE-F. Table 21 shows the inhibition of reverse-transcriptase activity from MSV (Moloney) and FLV (Friend) by DEAE-F. 

The mechanism of actions involves tubulin binding, reverse transcriptase inhibition, integrase inhibition and topoisomerase inhibition. Podophyllo-toxins bind to tubulin and are able to disrupt the cellular cytoskeleton and interfere with some vital virus processes. There is no relationship between the inhibition of reverse transcriptase (RT) and chemical structure in the case of lignans, because all the chemical antiviral structures are able to bind to the enzyme. As to the rest of the mechanism, there is not much information available. The effects of rabdosiin may be due to its topoisomerase inhibitory effects. Charlton concluded that the antiviral activity of lignans is not strong and that except for podophyllotoxin, which is used topically to treat various warts caused by HPV, none of them are of interest for commercial application. 

Sethi, M.L. Enzyme Inhibition. VIII Mode of Inhibition of Reverse Transcriptase Activity by Analogues, Isomers and Related Alkaloids of Coralyne. J. Pharm. Sci. 1985, 74, 889- 891. 

Emtricitabine 230 is an analogue of cytidine. The drug works by inhibiting of reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the enzyme that copies HIV RNA into new viral DNA. By interfering with this process, which is central to the replication of HIV, 230 can help to lower the amount of HIV, or viral load, in a patient s body and can indirectly increase the number of immune system cells (called T-cells or CD4+T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness. 

Ono K, Nakane H, Fukushima M, Chermann JC, Barre-Sinoussi F (1989) Inhibition of reverse transcriptase activity by a flavonoid compound, 5,6,7-trihydroxyflavone. Biochem Biophys Res Commun 160 982-987... 

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