Probing GFP Chromophore Analogs as Anti-HIV Agents Targeting LTR-III G-Quadruplex

Ryazantsev, D. Yu.; Myshkin, Mikhail Yu.; Alferova, Vera A.; Цветков, В. Б.; Shustova, Elena Y.; Kamzeeva, Polina N.; Kovalets, Polina V.; Zaitseva, Elvira R.; Балеева, Надежда С.; Zatsepin, Timofei S.; Шенкарев, Захар О.; Баранов, Михаил С.; Kozlovskaya, Liubov I.

doi:10.3390/biom11101409

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…The procedure is as previously described [ 36 ], with some changes. In brief, eight two-fold dilutions of 5 mM stock solutions of the compounds in RPMI-1640 (Chumakov FSC R&D IBP RAS, Russia) were prepared in two replicates.…”

Section: Methodsmentioning

confidence: 99%

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

et al. 2022

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Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations.

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Section: Methodsmentioning

confidence: 99%

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

et al. 2022

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“…The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/ijms25053054/s1. References [40][41][42][43][44] are cited in the Supplementary Materials Part S8.…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…The following supporting information can be downloaded at: . References [ 40 , 41 , 42 , 43 , 44 ] are cited in the Supplementary Materials Part S8.…”

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confidence: 99%

A Combination of Library Screening and Rational Mutagenesis Expands the Available Color Palette of the Smallest Fluorogen-Activating Protein Tag nanoFAST

Baleeva,

Bogdanova,

Goncharuk

et al. 2024

IJMS

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NanoFAST is the smallest fluorogen-activating protein, consisting of only 98 amino acids, used as a genetically encoded fluorescent tag. Previously, only a single fluorogen with an orange color was revealed for this protein. In the present paper, using rational mutagenesis and in vitro screening of fluorogens libraries, we expanded the color palette of this tag. We discovered that E46Q is one of the key substitutions enabling the range of possible fluorogens to be expanded. The introduction of this and several other substitutions has made it possible to use not only orange but also red and green fluorogens with the modified protein.

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“…Several anti-HIV-1 G4 ligands have been identified and characterized. Some of these ligands have shown potent and selective inhibitory effects on HIV-1 promoter activity and replication. ,− Anti-HIV-1 G4 ligands may thus offer a promising strategy to complement the current antiretroviral therapy and eradicate the latent viral reservoirs.…”

mentioning

confidence: 99%

Naphthalene Diimide–Tetraazacycloalkane Conjugates Are G-Quadruplex-Based HIV-1 Inhibitors with a Dual Mode of Action

Nadai,

Doria,

Frasson

et al. 2024

ACS Infect. Dis.

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Human immunodeficiency virus 1 (HIV-1) therapeutic regimens consist of three or more drugs targeting different steps of the viral life cycle to limit the emergence of viral resistance. In line with the multitargeting strategy, here we conjugated a naphthalene diimide (NDI) moiety with a tetraazacycloalkane to obtain novel naphthalene diimide (NDI)−tetraazacycloalkane conjugates. The NDI inhibits the HIV-1 promoter activity by binding to LTR G-quadruplexes, and the tetraazacycloalkane mimics AMD3100, which blocks HIV entry into cells by interfering with the CXCR4 coreceptor. We synthesized, purified, and tested the metal-free NDI−tetraazacycloalkane conjugate and the two derived metal−organic complexes (MOCs) that incorporate Cu 2+ and Zn 2+ . The NDI-MOCs showed enhanced binding to LTR G4s as assessed by FRET and CD assays in vitro. They also showed enhanced activity in cells where they dose-dependently reduced LTR promoter activity and inhibited viral entry only of the HIV-1 strain that exploited the CXCR4 coreceptor. The time of addition assay confirmed the dual targeting at the different HIV-1 steps. Our results indicate that the NDI-MOC conjugates can simultaneously inhibit viral entry, by targeting the CXCR4 coreceptor, and LTR promoter activity, by stabilizing the LTR G-quadruplexes. The approach of combining multiple targets in a single compound may streamline treatment regimens and improve the overall patient outcomes.

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Probing GFP Chromophore Analogs as Anti-HIV Agents Targeting LTR-III G-Quadruplex

Cited by 9 publications

References 42 publications

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

A Combination of Library Screening and Rational Mutagenesis Expands the Available Color Palette of the Smallest Fluorogen-Activating Protein Tag nanoFAST

Naphthalene Diimide–Tetraazacycloalkane Conjugates Are G-Quadruplex-Based HIV-1 Inhibitors with a Dual Mode of Action

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