Small Molecules Targeting Viral RNA
Abstract
:1. Introduction
2. How to Discover RNA-Targeting Antivirals
2.1. Understanding RNA Folding
2.2. In Silico Screening
2.3. Phenotypic Assays: Dual Luciferase Assays
2.4. Validation with WT Virus
3. Targetable Viral Elements
3.1. Frameshifting Element of SARS-CoV-2
3.2. Internal Ribosomal Entry Site
Target | Molecule | Identification | Activity |
---|---|---|---|
IRES (SL2) of EV71, CVA6, CVA7, EchoV7, CVB5 | Prunin [7] | Dual luciferase assay | Cells and mice with WT virus |
IRES (SL2) of EV71 | DMA-135 [74] | Fluorescent indicator displacement assay | Cells with WT virus |
IRES of EV71 | Kaempferol [69] | Dual luciferase assay | Cells with WT virus, mice [71] |
IRES of EV71, FMDV | Apigenin [83,84] | Targeted testing | Cells with WT virus, mice [71] |
IRES of EV71 | Idarubicin [85] | Screening with WT virus | Cells with WT virus |
IRES of EV71, EVD68, Echov6, CVA16, CVB1 | Emetin [72] | Screening with WT virus | Cells with WT virus, mice |
IRES of EV71, ECMV, HAV | Amantadine [75,76] | Dual luciferase assay, targeted testing | Cells with WT virus |
IRES of HCV (SL2a) | Benzimidazole derivatives [81,82] | Mass spectrometry on RNA model and structure–activity relationship | Screening with mass spectrometryActivity on replicon of HCV in cells |
IRES of HCV (SL2a) | DAP compounds [80] | Targeted design | Luciferase assay with IRES |
IRES of HCV | Geneticin [79] | Targeted testing | Cells with WT virus |
IRES (SL3a) of FMDV | IRAB [86] | Targeted design | Cells with WT virus |
3.3. RNA Elements of HIV
Target | Molecule | Identification | Activity |
---|---|---|---|
Frameshift site | RG501/DB213 [109,110] | Split luciferase assay | Cells with WT virus |
Frameshift site | Compounds 4 and 5 [92], N-methylated derivatives [94], triazole derivatives [95], and lower size derivatives [93] | Surface plasmon resonance on biotinylated RNA and chemical optimization | Cells with pseudotyped virus [92,94] and cells with WT virus [95] |
TAR | T0516-4834 [111] | In silico screening | Cells with pseudotyped virus |
TAR | Compound 4 [112] | Screening with targeted RNA | Cells with WT virus |
TAR | 6-Aminoquinolones [113] and derivatives [114,115] | Targeted testing | Cells with WT virus |
TAR | Netilmicin [10] | In silico screening | Cells with WT virus |
TAR | Acetylpromazine and Prochlorperazine [46,116] | In silico screening | Binding assay, Cells with coexpression of TAT/TAR [46] |
TAR | Furimidazoline/DB60 [117] | Targeted testing | Chronically infected cells |
TAR | Nucleobase-amino acid conjugates [118] | Targeted design | Cells with WT virus |
TAR | Compound 17 and 20 [119] | Targeted design | Cells with WT virus |
TAR | 460-G06 and 463-H08 [120] | Fluorescence resonance energy transfer | Cells with WT virus |
TAR | Amiloride derivatives [121,122] | Targeted testing and chemical optimization | Binding assay |
TAR | Purine substituted [123] | Targeted design | Cells with coexpression of TAT–TAR and with Simian Immunodeficiency Virus |
TAR | Aminoglycoside-arginine conjugates [124,125] | Targeted design | Binding assay and cells with Equine Infectious Anaemia Virus |
TAR | Compound 3ba and 3ca [126] | In situ cycloaddition | Fluorescence resonance energy transfer-based displacement assay |
RRE | Neomycin B [101,102,103,104,106] and conjugates [127], Neamine [104], and dimers [128] | Targeted testing, fluorescence anisotropy [104] | Cells chronically infected, [106] cells with WT virus [101,104] |
RRE | P-terphenyls substituted [129] | Targeted design | Cells with WT virus |
RRE | Mitoxantrone, clomiphene, ciprofloxacin and cyproheptadine [104], Compound 1a (benfluron), 1b, and 2a [130] | Fluorescence anisotropy | Cells with WT virus |
RRE | DB340, DB182, A132/DB247 [105,131,132] | Gel band shift assay | Binding assay |
Psi stem loop 3 | NSC260594 [107,108] | Fluorogenic destabilization assay | Cells with pseudotyped and WT virus |
4. Other Targets and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Molecule | Identification | Activity |
---|---|---|
MTDB [40,59,64] | In silico screening | Dual luciferase assay with −1 PRF sequence |
Merafloxacin [6,11,12] | Dual fluorescence screening | Cells with WT virus |
Geneticin [12] | Targeted testing | Cells and human-derived tissues with WT virus |
Aminoquinazoline derivatives [60] | Array screening | Dual luciferase/fluorescence assay with −1 PRF sequence |
C5 and C5-ribotac [61] | RNA-binding assay | Dual luciferase assay with −1 PRF sequence |
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Mathez, G.; Cagno, V. Small Molecules Targeting Viral RNA. Int. J. Mol. Sci. 2023, 24, 13500. https://doi.org/10.3390/ijms241713500
Mathez G, Cagno V. Small Molecules Targeting Viral RNA. International Journal of Molecular Sciences. 2023; 24(17):13500. https://doi.org/10.3390/ijms241713500
Chicago/Turabian StyleMathez, Gregory, and Valeria Cagno. 2023. "Small Molecules Targeting Viral RNA" International Journal of Molecular Sciences 24, no. 17: 13500. https://doi.org/10.3390/ijms241713500