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.
Highlights
Coronaviruses are enveloped RNA viruses of the Coronaviridae family that cause acute respiratory illness
A cytotoxicity assay was performed to clarify the non-toxic concentration of umifenovir in different cells that we used in our studies
Umifenovir was less toxic in GMK-AH-1(D) cells, with a CC50 value of 145.0 ± 5.0 μM (Figure 1A,C)
Summary
Coronaviruses are enveloped RNA viruses of the Coronaviridae family that cause acute respiratory illness. The Coronaviridae family constitutes the subfamily Orthocoronavirinae, classified into four CoV genera: Alphacoronavirus (alpha-CoV); Betacoronavirus (beta-CoV); Deltacoronavirus (delta-CoV); and Gammacoronavirus (gamma-CoV). Alphacoronaviruses include species of human coronavirus 229E and human coronavirus. Betacoronavirus genera are divided into four lineages (subgroups A,B,C,D). Subgroup A includes Betacoronavirus 1 (human coronavirus OC43). Human coronavirus HKU1 [1,2,3,4]. The most common seasonal respiratory infections can be caused by two species: HCoV-229E (α-Coronavirus) and HCoV-OC43
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