Aprotinin ‐ a new multi-target drug candidate or "magic shotgun" for the therapy of COVID‐19

Ivashchenko, A. V.; Svistunov, Andrey; Khorobryh, Tatiana; Логинов, Владимир; Karapetian, Ruben N.; Mishchenko, Natalia P.; Poyarkov, Stanislav; Topr, Michael; Волгин, Максим; Yakubova, Elena; Ivachtchenko, Alexandre V.

doi:10.21055/preprints-3111821

Cited by 4 publications

(4 citation statements)

References 28 publications

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“…APR has an antithrombotic mechanism of action, which, in combination with its multilevel anti-inflammatory activity, makes this drug a valuable assistant in COVID-19 treatment. APR can be used alone for the prevention and treatment of COVID-19 [59,66] or in combination with inhibitors of SARS-CoV-2 replication in the host cells [67,68,303,304].…”

Section: Entry Inhibitors Of Sars-cov-2mentioning

confidence: 99%

“…On the Covid19-preprints.microbe.ru platform, a published unreviewed preprint of a prospective clinical trial of the safety and efficacy of APR in the treatment of hospitalized patients with moderate-to-severe COVID-19 pneumonia has also been published [ 59 ]. This study included 23 patients (14 men and 9 women) with an average age of 60.7 ± 8.3 years.…”

Section: Apr For Covid-19 Treatmentmentioning

confidence: 99%

“…APR is a typical “magic shotgun” [ 59 , 60 , 61 , 62 ] pharmacological agent that reduces bleeding and limits the need for blood transfusion in cardiac and noncardiac surgeries [ 63 , 64 , 65 ]. It is also a promising drug in antiviral therapy [ 66 , 67 ] and especially in combination with other drugs [ 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

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Aprotinin—Drug against Respiratory Diseases

Ivachtchenko,

Ivashchenko,

Shkil

et al. 2023

IJMS

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Aprotinin (APR) was discovered in 1930. APR is an effective pan-protease inhibitor, a typical “magic shotgun”. Until 2007, APR was widely used as an antithrombotic and anti-inflammatory drug in cardiac and noncardiac surgeries for reduction of bleeding and thus limiting the need for blood transfusion. The ability of APR to inhibit proteolytic activation of some viruses leads to its use as an antiviral drug for the prevention and treatment of acute respiratory virus infections. However, due to incompetent interpretation of several clinical trials followed by incredible controversy in the literature, the usage of APR was nearly stopped for a decade worldwide. In 2015–2020, after re-analysis of these clinical trials’ data the restrictions in APR usage were lifted worldwide. This review discusses antiviral mechanisms of APR action and summarizes current knowledge and prospective regarding the use of APR treatment for diseases caused by RNA-containing viruses, including influenza and SARS-CoV-2 viruses, or as a part of combination antiviral treatment.

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Section: Entry Inhibitors Of Sars-cov-2mentioning

confidence: 99%

Section: Apr For Covid-19 Treatmentmentioning

confidence: 99%

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Aprotinin—Drug against Respiratory Diseases

Ivachtchenko,

Ivashchenko,

Shkil

et al. 2023

IJMS

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“…Thus, in addition to an anti-inflammatory effect, it is suggested that aprotinin can prevent SARS-CoV-2 penetration into susceptible cells and inhibits its replication. Our preliminary case series demonstrated a good potential of aprotinin for prevention [ 11 ] and as a part of combination therapy for the treatment [ 12 ] of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients

Ivashchenko¹,

Azarova

Egorova

et al. 2021

Viruses

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COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We studied the efficacy of Aprotinin (nonspecific serine proteases inhibitor) in combination with Avifavir® or Hydroxychloroquine (HCQ) drugs, which are recommended by the Russian Ministry of Health for the treatment therapy of moderate COVID-19 patients. This prospective single-center study included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2, and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU four times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). In cohorts 1–3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of the combination therapy in cohort 3 was the most prominent, and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0–4.0), normalization of the CRP concentration was 3.5 days (IQR 3–5), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1–3), improvement in clinical status or discharge from the hospital was 5 days (IQR 5–5), and improvement in lung lesions of patients on 14 day was 100%.

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Aprotinin is a potent multi-target drug for the combination therapy of moderate COVID-19 cases

Ivashchenko¹,

Azarova²,

Egorova³

et al. 2020

Preprint

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Objectives. COVID-19 is a contagious multisystem inflammatory disease caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have studied the efficacy of Aprotinin (nonspeciﬁc serine proteases inhibitor) and Avifavir or Hydroxychloroquine (HCQ) combinations for the therapy of COVID-19. Methods. Three prospective single-center (cohorts 1 – 3) studies included participants with moderate COVID-19-related pneumonia, laboratory-confirmed SARS-CoV-2 and admitted to the hospitals. Patients received combinations of intravenous (IV) Aprotinin (1,000,000 KIU daily, 3 days) and HCQ (cohort 1), inhalation (inh) treatment with Aprotinin (625 KIU 4 times per day, 5 days) and HCQ (cohort 2) or IV Aprotinin (1,000,000 KIU daily for 5 days) and Avifavir (cohort 3). Results. In the cohorts 1 – 3, the combination therapy showed 100% efficacy in preventing the transfer of patients (n = 30) to the intensive care unit (ICU). The effect of combination therapy in the cohort 3 was the most prominent and the median time to SARS-CoV-2 elimination was 3.5 days (IQR 3.0 – 4.0), normalization of CRP concentration was 3.5 days (IQR 3 – 5), of D-dimer concentration - 5 days (IQR 4 – 5); body temperature - 1 day (IQR 1 – 3), improvement in clinical status or discharge from the hospital - 5 days (IQR 5 – 5), and improvement in lung lesions of patients on 14 day - 100%. Conclusions. The administration of Aprotinin combinations prevented the transfer of moderate COVID-19 patients to the ICU for mechanical ventilation (ALV) or non-invasive ventilation (NIV) and by shortening of their hospital stay.

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Aprotinin ‐ a new multi-target drug candidate or "magic shotgun" for the therapy of COVID‐19

Abstract: Aprotinin showed high efficacy and safety in a prospective study of combination therapy for hospitalized patients with moderate to severe COVID-19 pneumonia.

Cited by 4 publications

References 28 publications

Aprotinin—Drug against Respiratory Diseases

Aprotinin—Drug against Respiratory Diseases

Effect of Aprotinin and Avifavir® Combination Therapy for Moderate COVID-19 Patients

Aprotinin is a potent multi-target drug for the combination therapy of moderate COVID-19 cases

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