Target-selective photo-degradation of HIV-1 protease by a fullerene-sugar hybrid

Tanimoto, Shuho; Sakai, Satoshi; Matsumura, Shuichi; Takahashi, Daisuke; Toshima, Kazunobu

doi:10.1039/b811726h

Cited by 58 publications

(39 citation statements)

References 23 publications

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“…Therefore, our data definitively demonstrate that fullerene derivatives fail to inhibit HIV-1 protease at doses that potently block HIV-1 maturation. These results conclusively show that fullerenes 1 and 2 are strongly anti-HIV active, but not via HIV-1 protease, contradicting the multiple studies previously reported (11,13,(18)(19)(20)(21)35).…”

Section: Characterization Of the Early Steps Of The Viral Life Cycle contrasting

confidence: 81%

“…Our data have corroborated the reported anti-HIV-1 activity of compounds 1 and 2 but do not support findings or predictions indicating reverse transcriptase (16) or protease (11,13,(18)(19)(20)(21)35) as their targets. Instead, we have demonstrated for the first time that fullerene inhibitors block HIV-1 maturation.…”

Section: Discussioncontrasting

confidence: 71%

“…In particular, compounds 1, 2, and 3 ( Fig. 1) have been shown to inhibit HIV-1 reverse transcriptase or protease in in vitro assays (11,16,18,35). Therefore, to fully characterize the anti-HIV-1 activity of fullerene derivatives in biologically relevant environments, compounds 1, 2, and 3 were evaluated for their ability to affect HIV-1 replication in human CD4 ϩ T cells (Fig.…”

Section: Effect Of Fullerene Derivatives On Hiv-1 Replication In Humamentioning

confidence: 99%

“…The first fullerene derivatives that exhibited anti-HIV activity were reported in 1993 (11,12). However, the lack of comprehensive characterization of the antiviral mechanisms of fullerene derivatives has hindered their further development into therapeutic drugs (9,(11)(12)(13)(14)(15)(16)(17)(18). Since the original report, it has been assumed that the anti-HIV activity of fullerene derivatives is mediated mainly, if not exclusively, by inhibition of the viral protease.…”

mentioning

confidence: 99%

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Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Martinez

Castro

Seong

et al. 2016

Antimicrob Agents Chemother

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Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4 ؉ T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4؉ T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors.

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Section: Characterization Of the Early Steps Of The Viral Life Cycle contrasting

confidence: 81%

Section: Discussioncontrasting

confidence: 71%

Section: Effect Of Fullerene Derivatives On Hiv-1 Replication In Humamentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Martinez

Castro

Seong

et al. 2016

Antimicrob Agents Chemother

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show abstract

“…The number of studies has steadily grown covering fundamental to applied fields of science and technology of fullerene chemistry. [1][2][3][4][5] Thus, C 60 and C 60 -based nanomaterials have been contributing to a variety of promising applications to protease inhibitors 6,7) , antibacterial 8) and anticancer 9) drugs in medicine, high surface area particles and supports in catalysis 10) , electron carriers in electronic devices 1) , and semiconductors in solar cells [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%