Antiviral activity of aminocaproic acid against SARS-CoV-2: review of the literature and results of the first experimental study

  • J. Chiaravalli Institut Pasteur, Paris, France https://orcid.org/0000-0001-9135-4565
  • A. Verneuil Institut Pasteur, Paris, France
  • V. Osiichuk Pharmaceutical Corporation “Yuria-Pharm” LLC, Kyiv, Ukraine
  • D. Golyshkin Pharmaceutical Corporation “Yuria-Pharm” LLC, Kyiv, Ukraine
  • O.Ya. Dziublyk National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the NAMS of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0001-5751-684X
  • M.I. Gumeniuk National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the NAMS of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0002-4365-6224
  • O.S. Denysov Communicable Diseases Intensive Care Association “INCURE”, Kyiv, Ukraine

Abstract

BACKGROUND. The SARS-CoV-2 pandemic has a significant impact on the global health care system, so effective treatments for coronavirus disease (COVID-19) are urgently needed. Nowadays, drug repurposing is widely considered for COVID-19 therapy; significant attention is paid to inhibitors of transmembrane serine proteases (TMPRSS2), which ensure the penetration of SARS-CoV-2 into the human cells and contribute to their infection. ε-aminocaproic acid (ACA), which has been used worldwide for many years to correct blood loss as a fibrinolysis inhibitor, is also known for its ability to block TMPRRS2. It is approved by the Ministry of Health of Ukraine for the treatment of influenza and acute respiratory viral infections.

OBJECTIVE. The aim of our study was to evaluate the antiviral effect of ACA in vitro by staining of SARS-CoV-2 viral antigen (spike protein) and by visual scoring of cytopathogenic effect (CPE).

RESULTS AND DISCUSSION. Using immunohistochemistry assay it was found that the mean value of EC50 for ACA on Caco-2 cells was 2.5 mg/ml and on Calu-3 cells – 17.3 mg/ml. Using CPE assay it was identified that the mean value of EC50 for ACA on Caco-2 cells was 6.4 mg/ml and on Calu-3 cells – 8.7 mg/ml. Additional analysis was shown that ACA has low cytotoxicity with CC50 values of >50 mg/ml on Caco-2 cells after 24h and 48h incubation and 37,57 and 41,29 mg/ml on Calu-3 cells after 24h and 48h incubation, respectively. Antiviral activity of ACA was detected when using non-toxic concentrations of the drug and did not depend on the time of introduction of ACA (before the introduction of the virus simultaneously with the pathogen after 1-hour incubation). ACA can be recommended for further in vivo studies on laboratory animals.

Keywords: SARS-CoV-2, COVID-19, transmembrane serine proteases, TMPRSS2 inhibitor, ε-aminocaproic acid

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Published
2022-10-24
How to Cite
Chiaravalli, J., Verneuil, A., Osiichuk, V., Golyshkin, D., Dziublyk, O., Gumeniuk, M., & Denysov, O. (2022). Antiviral activity of aminocaproic acid against SARS-CoV-2: review of the literature and results of the first experimental study. Infusion & Chemotherapy, (3), 5-12. https://doi.org/10.32902/2663-0338-2022-3-5-12
Section
ACTUAL PROBLEM

Author Biographies

J. Chiaravalli, Institut Pasteur, Paris, France

Jeanne Chiaravalli
Research engineer of the Institut Pasteur (chemogenomic and biological screening core facility, C2RT, departments of cell biology & infection and of structural biology & chemistry).

A. Verneuil, Institut Pasteur, Paris, France

Anne Huard de Verneuil
Institut Pasteur, chemogenomic and biological screening core facility, C2RT, departments of cell biology & infection and of structural biology & chemistry.

V. Osiichuk, Pharmaceutical Corporation “Yuria-Pharm” LLC, Kyiv, Ukraine

Osiichuk Viktoriia
Head of preclinical and clinical trials department, R&D Unit, Pharmaceutical corporation “Yuria-Pharm” LLC.
19, Sviatoslava Khorobroho st., Kyiv, 03151, Ukraine.

D. Golyshkin, Pharmaceutical Corporation “Yuria-Pharm” LLC, Kyiv, Ukraine

Golyshkin Dmytro
Preclinical trials senior specialist, R&D Unit, Pharmaceutical corporation “Yuria-Pharm” LLC.
PhD.
19, Sviatoslava Khorobroho st., Kyiv, 03151, Ukraine.

O.Ya. Dziublyk, National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the NAMS of Ukraine, Kyiv, Ukraine

Dziublyk Oleksandr Yaroslavovych
Head of the Department of technologies for the treatment of nonspecific lung diseases
MD, professor.
10, M. Amosova st., Kyiv, 03038, Ukraine.

M.I. Gumeniuk, National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky of the NAMS of Ukraine, Kyiv, Ukraine

Gumeniuk Mykola Ivanovych
Leading researcher of the Department of technologies of treatment of nonspecific lung diseases
MD, professor.
10, M. Amosova st., Kyiv, 03038, Ukraine.

O.S. Denysov, Communicable Diseases Intensive Care Association “INCURE”, Kyiv, Ukraine

Denysov Oleksii Serhiiovych
Executive director of the Public union “Communicable diseases intensive care association” (INCURE).
10, M. Amosova st., Kyiv, 03038, Ukraine.
E-mail: info@incure.info

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