In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2
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1. | Title | Title of document | In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2 |
2. | Creator | Author's name, affiliation, country |
A. N. Narovlyansky; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | M. V. Filimonova; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
N. G. Tsyshkova; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | A. V. Pronin; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | T. V. Grebennikova; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | E. V. Karamov; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | V. F. Larichev; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
G. V. Kornilayeva; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
I. T. Fedyakina; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | I. V. Dolzhikova; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
M. V. Mezentseva; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | E. I. Isaeva; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | V. V. Poloskov; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
L. S. Koval; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
V. P. Marinchenko; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
V. I. Surinova; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
A. S. Filimonov; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | A. A. Shitova; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
O. V. Soldatova; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | A. V. Sanin; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
I. K. Zubashev; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
A. V. Ponomarev; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country |
V. V. Veselovsky; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences ; Россия |
2. | Creator | Author's name, affiliation, country | V. V. Kozlov; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation; Gamasintez LLC ; Россия |
2. | Creator | Author's name, affiliation, country | A. V. Stepanov; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences ; Россия |
2. | Creator | Author's name, affiliation, country |
A. V. Khomich; Gamasintez LLC ; Россия |
2. | Creator | Author's name, affiliation, country | V. S. Kozlov; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | S. A. Ivanov; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | P. V. Shegai; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | A. D. Kaprin; National Medical Research Center for Radiology, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | F. I. Ershov; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
2. | Creator | Author's name, affiliation, country | A. L. Gintsburg; National Research Centre for Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya, Ministry of Health of the Russian Federation ; Россия |
3. | Subject | Discipline(s) | |
3. | Subject | Keyword(s) | SARS-CoV-2; indole-3 carboxylic acid derivative; antiviral activity; cell culture |
4. | Description | Abstract | The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012–2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility − high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) − this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment. |
5. | Publisher | Organizing agency, location | Acta Naturae Ltd |
6. | Contributor | Sponsor(s) |
Ministry of Health of the Russian Federation (056-00119-21-00) |
7. | Date | (DD-MM-YYYY) | 17.01.2024 |
8. | Type | Status & genre | Peer-reviewed Article |
8. | Type | Type | Research Article |
9. | Format | File format | |
10. | Identifier | Uniform Resource Identifier | https://actanaturae.ru/2075-8251/article/view/26623 |
10. | Identifier | Digital Object Identifier (DOI) | 10.32607/actanaturae.26623 |
11. | Source | Title; vol., no. (year) | Acta Naturae; Vol 15, No 4 (2023) |
12. | Language | English=en | en |
13. | Relation | Supp. Files |
Fig. 1. 6-Bromo-1-methyl-5-methoxy-2-(1-piperidinomethyl)-3-(2-diethylamino ethoxy)carbonylindole dihydrochloride (compound 1) (53KB) doi: 10.32607/20758251-2023-15-4-83-91-130344 Fig. 2. Reagents and conditions: a. (1) aq. NaOH, dioxane; (2) Me2SO4, 20°C; b. N-bromosuccinimide, CCl4, boiling; c. N-bromosuccinimide, (PhCOO)2, CCl4, irradiation (100 W bulb), boiling; d. piperidine, PhH, 20°C; e. (1) aq. NaOH, EtOH, boiling; (2) HCl (conc.); f. SOCl2, dioxane, DMFA (cat.), 60°C; g. (1) Et2NCH2CH2OH, Et3N, PhH, boil.; (2) HCl, Et2O, acetone, 20°C (361KB) doi: 10.32607/20758251-2023-15-4-83-91-130345 Fig. 3. IR spectrum of compound 1 (134KB) doi: 10.32607/20758251-2023-15-4-83-91-130346 Fig. 4. 1H NMR spectrum of compound 1 (113KB) doi: 10.32607/20758251-2023-15-4-83-91-130347 Fig. 5. Mass spectrum of compound 1 (98KB) doi: 10.32607/20758251-2023-15-4-83-91-130348 Fig. 6. Determining the cytotoxic effect of compound 1 96 h after its addition to the Vero E6 cell culture (using MTS vital dye). СС50 = 83.32 µg/mL (114KB) doi: 10.32607/20758251-2023-15-4-83-91-130349 |
14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
15. | Rights | Copyright and permissions |
Copyright (c) 2024 Narovlyansky A.N., Filimonova M.V., Tsyshkova N.G., Pronin A.V., Grebennikova T.V., Karamov E.V., Larichev V.V., Kornilayeva G.V., Fedyakina I.T., Dolzhikova I.V., Mezentseva M.V., Isaeva E.I., Poloskov V.V., Koval L.S., Marinchenko V.P., Surinova V.I., Filimonov A.S., Shitova A.A., Soldatova O.V., Sanin A.V., Zubashev I.K., Ponomarev A.V., Veselovsky V.V., Kozlov V.V., Stepanov A.V., Khomich A.V., Kozlov V.S., Ivanov S.A., Shegai P.V., Kaprin A.D., Ershov F.I., Gintsburg A.L.![]() This work is licensed under a Creative Commons Attribution 4.0 International License. |