In Vitro Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2.

Journal: Acta naturae
Published Date: Jan 1, 2023

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 . 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 (IC = 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.

Authors

  • 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, Moscow, 123098 Russian Federation.
  • M V Filimonova
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • N G Tsyshkova
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • L S Koval
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • V P Marinchenko
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • V I Surinova
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • A S Filimonov
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • A A Shitova
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • O V Soldatova
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • V V Veselovsky
    N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • A V Stepanov
    N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russian Federation.
  • A V Khomich
    Gamasintez LLC, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • S A Ivanov
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • P V Shegai
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • A D Kaprin
    National Medical Research Center for Radiology, Ministry of Health of the Russian Federation, Obninsk, 249036 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.
  • 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, Moscow, 123098 Russian Federation.

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