{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T02:15:59Z","timestamp":1777947359984,"version":"3.51.4"},"reference-count":17,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u00ae 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\u20133, 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\u20134.0), normalization of the CRP concentration was 3.5 days (IQR 3\u20135), of the D-dimer concentration was 5 days (IQR 4 to 5); body temperature was 1 day (IQR 1\u20133), improvement in clinical status or discharge from the hospital was 5 days (IQR 5\u20135), and improvement in lung lesions of patients on 14 day was 100%.<\/jats:p>","DOI":"10.3390\/v13071253","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T23:57:22Z","timestamp":1624838242000},"page":"1253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect of Aprotinin and Avifavir\u00ae Combination Therapy for Moderate COVID-19 Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Andrey A.","family":"Ivashchenko","sequence":"first","affiliation":[{"name":"ChemRar High-Tech Center, 141401 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria N.","family":"Azarova","sequence":"additional","affiliation":[{"name":"IPHARMA LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0405-9590","authenticated-orcid":false,"given":"Alina N.","family":"Egorova","sequence":"additional","affiliation":[{"name":"IPHARMA LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben N.","family":"Karapetian","sequence":"additional","affiliation":[{"name":"ChemRar Research Institute, 141401 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dmitry V.","family":"Kravchenko","sequence":"additional","affiliation":[{"name":"Chemical Diversity Research Institute, 141401 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia V.","family":"Krivonos","sequence":"additional","affiliation":[{"name":"IPHARMA LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir G.","family":"Loginov","sequence":"additional","affiliation":[{"name":"JSC \u201cSpecial Economic Zones\u201d, 125009 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislav V.","family":"Poyarkov","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning of the Federal Medical-Biological Agency (FMBA), 119121 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Merkulova","sequence":"additional","affiliation":[{"name":"IPHARMA LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga S.","family":"Rosinkova","sequence":"additional","affiliation":[{"name":"Clinical Hospital No. 1, 214006 Smolensk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay P.","family":"Savchuk","sequence":"additional","affiliation":[{"name":"Chemical Diversity Research Institute, 141401 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail A.","family":"Topr","sequence":"additional","affiliation":[{"name":"ChemDiv Inc., San Diego, CA 92121-3103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena N.","family":"Simakina","sequence":"additional","affiliation":[{"name":"Clinical Hospital No. 1, 214006 Smolensk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Yakubova","sequence":"additional","affiliation":[{"name":"Chromis LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre V.","family":"Ivachtchenko","sequence":"additional","affiliation":[{"name":"ChemRar High-Tech Center, 141401 Moscow, Russia"},{"name":"Chromis LLC, Skolkovo Innovative Centre, 121205 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"ref_1","unstructured":"COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Available online: https:\/\/publichealthupdate.com\/jhu\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4813","DOI":"10.1111\/bph.15072","article-title":"Current pharmacological treatments for COVID-19: What\u2019s next?","volume":"177","author":"Scavone","year":"2020","journal-title":"Br. 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