Inhibitory Effect of Lithospermic Acid on the HIV-1 Nucleocapsid Protein

被引:6
作者
Mori, Mattia [1 ]
Ciaco, Stefano [1 ,2 ]
Mely, Yves [2 ]
Karioti, Anastasia [3 ]
机构
[1] Univ Siena, Dept Biotechnol Chem & Pharm, Via Aldo Moro 2, I-53100 Siena, Italy
[2] Univ Strasbourg, Fac Pharm, UMR CNRS 7021, Lab Bioimagerie & Pathol, 74 Route Rhin, F-67401 Illkirch Graffenstaden, France
[3] Aristotle Univ Thessaloniki, Sch Pharm, Lab Pharmacognosy, Thessaloniki 54124, Greece
来源
MOLECULES | 2020年 / 25卷 / 22期
关键词
lithospermic acid; nucleocapsid protein; catechol; natural products; HIV; molecular modeling; fluorescence-based assays; STRUCTURAL-CHARACTERIZATION; IDENTIFICATION; COMPLEX; POTENT; INTEGRATION; TARGET; NCP7;
D O I
10.3390/molecules25225434
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The HIV-1 nucleocapsid protein (NC) is a desirable target in antiretroviral therapy due to its high conservation among HIV-1 strains, and to its multiple and crucial roles in the HIV-1 replication cycle. Natural products represent a valuable source of NC inhibitors, with the catechol group being a privileged scaffold in NC inhibition. By coupling molecular modeling with NMR spectroscopy and fluorescence-based assays, we disclosed lithospermic acid, a catechol derivative extracted from Salvia miltiorrhizza, as a potent and chemically stable non-covalent inhibitor of the NC. Being different from other catechol derivative reported so far, lithospermic acid does not undergo spontaneous oxidation in physiological conditions, thus becoming a profitable starting point for the development of efficient NC inhibitors.
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页数:11
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共 51 条
  • [1] Isolation of two highly potent and non-toxic inhibitors of human immunodeficiency virus type 1 (HIV-1) integrase from Salvia miltiorrhiza
    Abd-Elazem, IS
    Chen, HS
    Bates, RB
    Huang, RCC
    [J]. ANTIVIRAL RESEARCH, 2002, 55 (01) : 91 - 106
  • [2] Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review
    Akram, Muhammad
    Tahir, Imtiaz Mahmood
    Shah, Syed Muhammad Ali
    Mahmood, Zahed
    Altaf, Awais
    Ahmad, Khalil
    Munir, Naveed
    Daniyal, Muhammad
    Nasir, Suhaila
    Mehboob, Huma
    [J]. PHYTOTHERAPY RESEARCH, 2018, 32 (05) : 811 - 822
  • [3] NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the Ψ-RNA packaging signal.: Implications for genome recognition
    Amarasinghe, GK
    De Guzman, RN
    Turner, RB
    Chancellor, KJ
    Wu, ZR
    Summers, MF
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2000, 301 (02) : 491 - 511
  • [4] [Anonymous], QUACPAC 2 0 0 3
  • [5] [Anonymous], SZYBKI 1 10 0 3
  • [6] [Anonymous], VIDA 4 4 0 4
  • [7] Potential of selected Lamiaceae plants in anti(retro)viral therapy
    Bekut, Maja
    Brkic, Snezana
    Kladar, Nebojsa
    Dragovic, Gordana
    Gavaric, Neda
    Bozin, Biljana
    [J]. PHARMACOLOGICAL RESEARCH, 2018, 133 : 301 - 314
  • [8] HIV-1 nucleocapsid protein activates transient melting of least stable parts of the secondary structure of TAR and its complementary sequence
    Bernacchi, S
    Stoylov, S
    Piémont, E
    Ficheux, D
    Roques, BP
    Darlix, JL
    Mély, Y
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2002, 317 (03) : 385 - 399
  • [9] Coupled integration of human immunodeficiency virus type 1 cDNA ends by purified integrase in vitro: Stimulation by the viral nucleocapsid protein
    Carteau, S
    Gorelick, RJ
    Bushman, FD
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (08) : 6670 - 6679
  • [10] Human immunodeficiency virus type 1 nucleocapsid protein specifically stimulates Mg2+-dependent DNA integration in vitro
    Carteau, S
    Batson, SC
    Poljak, L
    Mouscadet, JF
    DeRocquigny, H
    Darlix, JL
    Roques, BP
    Kas, E
    Auclair, C
    [J]. JOURNAL OF VIROLOGY, 1997, 71 (08) : 6225 - 6229