Antiviral Activity of Umifenovir In Vitro against a Broad Spectrum of Coronaviruses, Including the Novel SARS-CoV-2 Virus

Abstract

An escalating pandemic of the novel SARS-CoV-2 virus is impacting global health, and effective antivirals are needed. Umifenovir (Arbidol) is an indole-derivative molecule, licensed in Russia and China for prophylaxis and treatment of influenza and other respiratory viral infections. It has been shown that umifenovir has broad spectrum activity against different viruses. We evaluated the sensitivity of different coronaviruses, including the novel SARS-CoV-2 virus, to umifenovir using in vitro assays. Using a plaque assay, we revealed an antiviral effect of umifenovir against seasonal HCoV-229E and HCoV-OC43 coronaviruses in Vero E6 cells, with estimated 50% effective concentrations (EC50) of 10.0 ± 0.5 µM and 9.0 ± 0.4 µM, respectively. Umifenovir at 90 µM significantly suppressed plaque formation in CMK-AH-1 cells infected with SARS-CoV. Umifenovir also inhibited the replication of SARS-CoV-2 virus, with EC50 values ranging from 15.37 ± 3.6 to 28.0 ± 1.0 µM. In addition, 21–36 µM of umifenovir significantly suppressed SARS-CoV-2 virus titers (≥2 log TCID50/mL) in the first 24 h after infection. Repurposing of antiviral drugs is very helpful in fighting COVID-19. A safe, pan-antiviral drug such as umifenovir could be extremely beneficial in combating the early stages of a viral pandemic.

Experimental Models of COVID-19

“…Vero E6 cells were recently used in a study determining the in vitro minimal exposure time and viral concentration needed to establish persistent SARS-CoV-2 infection ( Zupin et al., 2021 ). Vero E6 cell lines have also been used in multiple studies of SARS-CoV-2 repurposed antivirals ( Canal et al., 2021 , Leneva et al., 2021 ), protease inhibitors ( Cui and Jia, 2021 ; Han et al., 2021 ) as well as inhibiting peptides ( Kelesidis et al., 2021 ). This cell line model was used in research investigating the indirect inhibition of the ACE-2 receptor as a possible SARS-CoV-2 therapeutic ( Tanimoto et al., 2021 ) along with human polyclonal IgG ( Gilliland et al., 2021 ).…”

Pharmacoepidemiological research of COVID-19 in the Russian Federation EGIDA-2020

“…УМФпротивовирусный препарат широкого спектра действия, применяемый в России и Китае. Изучение противовирусной активности в культуре клеток Vero показало, что УМФ обладает специфической активностью в отношении вируса SARS-CoV-2 [18] и способен значительно снижать патологическое воздействие вируса на клетки [19]. Также УМФ активен в отношении других коронавирусов: SARS-CoV, сезонных коронавирусов [18] и MERS-CoV [15].…”

“…Изучение противовирусной активности в культуре клеток Vero показало, что УМФ обладает специфической активностью в отношении вируса SARS-CoV-2 [18] и способен значительно снижать патологическое воздействие вируса на клетки [19]. Также УМФ активен в отношении других коронавирусов: SARS-CoV, сезонных коронавирусов [18] и MERS-CoV [15]. УМФ относится к противовирусным препаратам, ингибирующим процесс слияния вирусов с клеткой.…”

The role of lipids in the pathophysiology of coronavirus infections

“…Phytosterols can affect viral infection by decreasing the levels of cholesterol in cell membrane [ 71 ]. In this regard, umifenovir and chloroquine are antiviral drugs that inhibit the process of endocytosis [ 72 ]. The mechanism of actions of these antiviral drugs suggests the significance of the viral membrane for developing potent drugs.…”