Comparative studies of the inhibitory properties of antibiotics on human immunodeficiency virus and avian myeloblastosis virus reverse transcriptases and cellular DNA polymerases.

Abstract

The inhibition of humanimmunodeficiency virus (HIV) reverse transcriptase by certain antibiotics and related compounds was studied in comparisonwith that of avian myeloblastosis virus (AMV)reverse transcriptase and cellular DNApolymerases a and £. In general, compoundsthat inhibited HIVreverse transcriptase also inhibited AMV reverse transcriptase. For example, 10^g/ml of the isoquinoline quinones used in this study inhibited approximately 80 % of the activity of reverse transcriptases of HIV and AMV,but did not inhibit the activity of DNApolymerases a and fi even at 50^g/ml. AMV enzymewas more sensitive than HIV enzyme to colistin, enduracidins A and B, janiemycin, glysperin A, and thielavins A and B. The streptonigrin alkyl esters, however, inhibited HIVreverse transcriptase only. Sakyomicin A, luzopeptins, ellagic acid and suramine inhibited the activities of reverse transcriptases and cellular DNApolymerases.Reverse transcription, a step catalyzed by the unique DNApolymerase, reverse transcriptase, is a pivotal step in the replication of retroviruses and in the stable inheritance of viral genome. An effective inhibitor of reverse transcriptase may selectively block viral replication and therefore, the enzyme has been one of the molecular targets in antiviral studies for manyyears. We have undertaken a search for inhibitors of avian myeloblastosis virus (AMV)reverse transcriptase among antibiotics and related compounds. Humanimmunodeficiency virus (HIV), a causative agent for acquired im- Materials and Methods MaterialsAMV reverse transcriptase was purchased from Seikagaku KogyoCo., Ltd. HIV reverse trans-

Antitumour Quinones

“…Because of that these quadruplex structures are considered to be promising targets for drug Many different approaches have been undertaken to inhibit telomerase activity up to now, for instance the design of antisense oligonucleotides or nucleoside analogue reverse transcriptase inhibitors [239]. Among the quinones some antibiotics such as streptonigrin and sarkomycin, A were shown to inhibit reverse transcriptase units of retroviral telomerase [240,241]. Interesting structures with strong human telomerase inhibitory effects in a modified telomeric repeat amplification protocol (TRAP) are found among the rubromycins (76)- (79), quinoid compounds containing benzofuran and benzodipyran rings forming spiroketals [242].…”

Direct comparisons of inhibitor sensitivities of reverse transcriptases from feline and human immunodeficiency viruses

“…In contrast, FIV RT was much different from avian myeloblastosis virus RT in sensitivity to these inhibitors (12). Moreover, Take et al (15) have shown that the HIV and avian myeloblastosis virus RTs are different in their sensitivities to many inhibitors. We subsequently purified FIV RT and showed that it is also similar to HIV RT in physical properties, template specificities, and requirements for Mg2+ (11 Poly(rA)-oligo(dT)1o and the RNA homopolymers and DNA primers used to make poly(rI)-oligo(dC)10 and poly (rC)-oligo(dG)1o were purchased from Pharmacia LKB.…”

Inhibition of HIV-1 RNase H Activity by Nucleotide Dimers and Monomers

“…This suggests inhibitors of this group may target a conserved portion of RT unique to HIV/FIV. It has been shown by others that HIV RT inhibitors are not necessarily effective against AMV RT (Take et al, 1988). MuLV was inhibited minimally by dimer A1 and A16 but 60% by A15 at 50flM.…”