Newly Synthesizedl-Enantiomers of 3'-Fluoro-Modified β-2'-Deoxyribonucleoside 5'-Triphosphates Inhibit Hepatitis B DNA Polymerases But Not the Five Cellular DNA Polymerases α, β, γ, δ, and ε Nor HIV-1 Reverse Transcriptase

1998 ◽  
Vol 41 (12) ◽  
pp. 2040-2046 ◽  
Author(s):  
Martin von Janta-Lipinski ◽  
Burkhardt Costisella ◽  
Hansueli Ochs ◽  
Ulrich Hübscher ◽  
Peter Hafkemeyer ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Dna Polymerases ◽  
Cellular Dna ◽  
Hiv 1

scholarly journals Mode of inhibition of HIV reverse transcriptase by 2-hexaprenylhydroquinone, a novel general inhibitor of RNA-and DNA-directed DNA polymerases

1997 ◽  
Vol 324 (3) ◽  
pp. 721-727 ◽  
Author(s):  
Shoshana LOYA ◽  
Amira RUDI ◽  
Yoel KASHMAN ◽  
Amnon HIZI
Keyword(s):  
Reverse Transcriptase ◽  
Dna Polymerases ◽  
Competitive Inhibitor ◽  
Polymerization Process ◽  
Hiv Reverse Transcriptase ◽  
Allosteric Site ◽  
Leukaemia Virus ◽  
General Inhibitor ◽  
Hiv 1 ◽  
Rna And Dna

A natural compound from the Red Sea sponge Ircinia sp., 2-hexaprenylhydroquinone (HPH), has been shown to be a general inhibitor of retroviral reverse transcriptases (from HIV-1, HIV-2 and murine leukaemia virus) as well as of cellular DNA polymerases (Escherichia coli DNA polymerase I, and DNA polymerases α and β). The pattern of inhibition was found to be similar for all DNA polymerases tested. Thus the mode of inhibition was studied in detail for HIV-1 reverse transcriptase. HPH is a non-competitive inhibitor and binds the enzyme irreversibly with high affinity (Ki = 0.62 μM). The polar hydroxy groups have been shown to be of key importance. A methylated derivative, mHPH, which is devoid of these polar moieties, showed a significantly decreased capacity to inhibit all DNA polymerases tested. Like the natural product, mHPH binds the enzyme independently at an allosteric site, but with reduced affinity (Ki = 7.4 μM). We show that HPH does not interfere with the first step of the polymerization process, i.e. the physical formation of the reverse-transcriptase–DNA complex. Consequently, we suggest that the natural inhibitor interferes with the subsequent steps of the overall reaction. Since HPH seems not to affect the affinity of dNTP for the enzyme (the Km is unchanged under conditions where the HPH concentration is increased), we speculate that its inhibitory capacity is derived from its effect on the nucleotidyl-transfer catalytic reaction. We suggest that such a mechanism of inhibition is typical of an inhibitor whose mode of inhibition should be common to all RNA- and DNA-directed polymerases.

scholarly journals Delayed Chain Termination Protects the Anti-hepatitis B Virus Drug Entecavir from Excision by HIV-1 Reverse Transcriptase

2008 ◽  
Vol 283 (49) ◽  
pp. 34218-34228 ◽  
Author(s):  
Egor P. Tchesnokov ◽  
Aleksandr Obikhod ◽  
Raymond F. Schinazi ◽  
Matthias Götte
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Chain Termination ◽  
B Virus ◽  
Hiv 1

scholarly journals Inhibition of Reverse Transcriptase as A Clue for Curing RNA Viral Infections

2020 ◽  
Vol 5 (6) ◽  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Reverse Transcriptase ◽  
Viral Infections ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Plausible Mechanism ◽  
Hiv 1

Scientists provide evidence showing that delayed chain discontinuation is a plausible mechanism of action of Remdesivir. This mechanism was described previously in the context of reverse transcriptase (RT) inhibition of human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus

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