Enisamium is an inhibitor of the SARS-CoV-2 RNA polymerase and shows improvement of recovery in COVID-19 patients in an interim analysis of a clinical trial.

Autor:	Holubovska O; O.O. Bogomolets National Medical University, T. Shevchenko blvd., 13, Kyiv, Ukraine.; These authors contributed equally., Bojkova D; Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.; These authors contributed equally., Elli S; Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', Via Giuseppe Colombo 81, 20133 Milano, Italy.; These authors contributed equally., Bechtel M; Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany., Boltz D; IIT Research institute, 10 W 35th St, Chicago, IL 60616, United States., Muzzio M; IIT Research institute, 10 W 35th St, Chicago, IL 60616, United States., Peng X; IIT Research institute, 10 W 35th St, Chicago, IL 60616, United States., Sala F; Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', Via Giuseppe Colombo 81, 20133 Milano, Italy., Cosentino C; Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', Via Giuseppe Colombo 81, 20133 Milano, Italy., Mironenko A; L.V. Gromashevsky Institute of Epidemiology and Infectious Diseases of the NAMS of Ukraine, Department of respiratory and other viral infections, Amosova str 5a, 03083, Kyiv, Ukraine., Milde J; Pharmalog Institut für klinische Forschung GmbH, Ismaning, Germany., Lebed Y; Pharmaxi LLC, Filatova Str., 10A, office 3/20, 01042, Kyiv, Ukraine., Stammer H; Pharmalog Institut für klinische Forschung GmbH, Ismaning, Germany., Goy A; Farmak Joint Stock Company, Kyrylivska Street, 04080, Kyiv, Ukraine., Guerrini M; Istituto di Ricerche Chimiche e Biochimiche 'G. Ronzoni', Via Giuseppe Colombo 81, 20133 Milano, Italy., Mueller L; Dr. Regenold GmbH, Zöllinplatz 4, D-79410 Badenweiler, Germany., Cinatl J; Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany., Margitich V; Farmak Joint Stock Company, Kyrylivska Street, 04080, Kyiv, Ukraine., Te Velthuis AJW; Division of Virology, Department of Pathology, Addenbrooke's Hospital, University of Cambridge, Hills Road, CB2 2QQ, United Kingdom.; These authors contributed equally.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2021 Jan 21. Date of Electronic Publication: 2021 Jan 21.
DOI:	10.1101/2021.01.05.21249237
Abstrakt:	Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called Coronavirus Disease 2019 (COVID-19). Control of SARS-CoV-2 spread will depend on vaccine-induced or naturally acquired protective herd immunity. Until then, antiviral strategies are needed to manage COVID-19, but approved antiviral treatments, such as remdesivir, can only be delivered intravenously. Enisamium (laboratory code FAV00A, trade name Amizon®) is an orally active inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. Here we show that enisamium can inhibit SARS-CoV-2 infections in NHBE and Caco-2 cells. In vitro , the previously identified enisamium metabolite VR17-04 directly inhibits the activity of the SARS-CoV-2 RNA polymerase. Docking and molecular dynamics simulations suggest that VR17-04 prevents GTP and UTP incorporation. To confirm enisamium's antiviral properties, we conducted a double-blind, randomized, placebo-controlled trial in adult, hospitalized COVID-19 patients, which needed medical care either with or without supplementary oxygen. Patients received either enisamium (500 mg per dose) or placebo for 7 days. A pre-planned interim analysis showed in the subgroup of patients needing supplementary oxygen (n = 77) in the enisamium group a mean recovery time of 11.1 days, compared to 13.9 days for the placebo group (log-rank test; p=0.0259). No significant difference was found for all patients (n = 373) or those only needing medical care (n = 296). These results thus suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis and that enisamium treatment shortens the time to recovery for COVID-19 patients needing oxygen. Competing Interests: Conflict of interest V.M. and A.G. are employees of Farmak Public Joint Stock Company, Kiev, Ukraine. Part of this research was funded by Farmak Public Joint Stock Company, Kiev, Ukraine.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu