Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug 23;13(8):1665.
doi: 10.3390/v13081665.

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

Irina Leneva  1 , Nadezhda Kartashova  1 , Artem Poromov  1 , Anastasiia Gracheva  1 , Ekaterina Korchevaya  1 , Ekaterina Glubokova  1 , Olga Borisova  1 , Anna Shtro  2 , Svetlana Loginova  1 , Veronika Shchukina  1 , Ravil Khamitov  3 , Evgeny Faizuloev  1
Affiliations

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

Irina Leneva et al. Viruses. .

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.

Keywords: SARS-CoV; SARS-CoV-2; antiviral activity; coronaviruses; umifenovir.

PubMed Disclaimer

Conflict of interest statement

The authors declare no financial or commercial conflicts of interest.

Figures

Figure 1
Figure 1
Cytotoxicity of antivirals in different cell lines. Vero E6, GMK-AH-1(D), and Vero CCL81 cells were seeded into 96-well microtiter plates and incubated until formation of a confluent monolayer. Umifenovir (A), ribavirin, and hydroxychloroquine (B) were added at various concentrations. The impact of treatment on cell viability was assessed by MTT assay after 72 h incubation. CC10 and CC50 values were generated and represented as mean ± SD (C). The three-parameter log-logistic (LL.3) function was used. 1 CC10 and CC50 were determined from three independent experiments.
Figure 2
Figure 2
Antiviral activity of umifenovir against seasonal coronaviruses. Umifenovir (UMF) and hydroxychloroquine (HCQ) were added to Vero E6 cells at each concentration. The rate of cell viability (cytotoxicity control) was measured after 72 h using the MTT assay. HCoV-OC43 and HCoV-229E virus growth was determined by plaque assay 8 days after infection in the presence of various concentrations of drugs. (A) Percent inhibition of HCoV-OC43 by umifenovir (UMF+V) and hydroxychloroquine (HCQ+V) and cytotoxicity (UMF, HCQ) in Vero E6. (B) Percent inhibition of HCoV-229E by umifenovir (UMF+V) and cytotoxicity (UMF) in Vero E6. (C) The CC50 and EC50 values are represented as mean ± SD, and the three-parameter log-logistic (LL.3) function was used. Selectivity index (SI) was calculated as a ratio of a drug’s CC50 and EC50 values (SI = CC50/EC50). 1 CC50 and EC50 were determined from three independent experiments.
Figure 3
Figure 3
Effects of pre- and post-exposure with umifenovir on SARS-CoV viral titers. SARS-CoV-infected GMK-AH-1(D) cells were incubated with umifenovir (90 µM) 4 h before, immediately after, and 2 h after infection. Viral titers (log PFU/mL) are shown as mean ± SD. Differences between virus control group and treated groups: * p < 0.05, ** p < 0.01. Kruskal–Wallis test.
Figure 4
Figure 4
Antiviral activity of umifenovir against SARS-CoV-2 virus. Umifenovir (UMF) and hydroxychloroquine (HCQ) were added to Vero CCL81 cells at various concentrations. The cellular cytotoxicity test of Vero CCL81 cells was included in the experiment, and the resulting curves are shown (UMF, HCQ). After 2 h of incubation, virus at dose of 0.001 (A) and 0.005 MOI (B) was added to wells, except ‘cell control’ wells, and cells were incubated at 37 °C in a humidified 5% CO2 atmosphere for 5 days. The CPE and rate of cell viability was measured using MTT assay. (A) Percent inhibition of SARS-CoV-2 (strain Dubrovka) by umifenovir (UMF+V) and hydroxychloroquine (HCQ+V) at MOI 0.001 and cytotoxicity (UMF, HCQ). (B) Percent inhibition of SARS-CoV-2 (strain Dubrovka) by umifenovir (UMF+V) and hydroxychloroquine (HCQ+V) at MOI 0,005) and cytotoxicity (UMF,HCQ). (C) The EC50 values are represented as mean ± SD; the three-parameter log-logistic (LL.3) function was used.
Figure 5
Figure 5
Effects of low and high multiplicity of infection on umifenovir antiviral activity. SARS-CoV-2 Dubrovka strain-infected Vero CCL81 cells were pre-treated with 31.5 µM umifenovir for 2 h at 0.001 and 0.005 MOI. After incubation for 5 days at 37 °C in a humidified 5% CO2 atmosphere, the cell viability was estimated by MTT assay. The optical density (OD) is shown as the mean ± SD. Data represent three replications. Cell control—1.59 ± 0.42 (n = 6), umifenovir control (without virus)—1.47 ± 0.54 (n = 3).
Figure 6
Figure 6
Effect of pre- and post-exposure treatment on antiviral activity of umifenovir. Umifenovir at dose 31.5 µM was added to Vero CCL81 cells. After incubation for 24 and 2 h, the virus (SARS-CoV-2 Dubrovka strain 0.001 MOI) was added. For post-exposure treatment Vero CCL81 cells were infected with the same dose of virus. Umifenovir at a concentration of 31.5 µM was then added 24, 48, or 96 h after infection.
Figure 7
Figure 7
Effect of umifenovir and hydroxychloroquine (HCQ) on viral titers in SARS-CoV-2-infected Vero CCL81 cells at low and high multiplicities of infection. Vero CCL81 cells were pre-treated with drugs for 2 h, and virus at doses of 0.001 and 0.005 MOI was then added. After incubation or 24 h, the culture supernatants were collected to quantify viral loads by titration using the tissue culture infectious dose 50 (TCID50) method. The viral titers (log TCID50/mL) are shown as mean ± SD. Data represent three independent experiments. Differences between virus control group and treated groups: * p < 0.05, ** p < 0.01. Kruskal–Wallis test. n.d.—not determined.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Woo P.C., Lau S.K., Huang Y., Yuen K.Y. Coronavirus diversity, phylogeny and interspecies jumping. Exp. Biol. Med. 2009;234:1117–1127. doi: 10.3181/0903-MR-94. - DOI - PubMed
    1. Pal M., Berhanu G., Desalegn C., Kandi V. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update. Cureus. 2020;12:e7423. doi: 10.7759/cureus.7423. - DOI - PMC - PubMed
    1. Avis B.M., Foxman B., Monto A.S., Baric R.S., Martin E.T., Uzicanin A., Rainey J.J., Aiello A.E. Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding. Influenza Other Respir. Viruses. 2018;12:582–590. - PMC - PubMed
    1. Hendley J.O., Fishburne H.B., Gwaltney J.M., Jr. Coronavirus infections in working adults. Eight-year study with 229 E and OC 43. Am. Rev. Respir. Dis. 1972;105:805–811. - PubMed
    1. Cheng V.C., Lau S.K., Woo P.C., Yuen K.Y. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin. Microbiol. Rev. 2007;20:660–694. doi: 10.1128/CMR.00023-07. - DOI - PMC - PubMed

MeSH terms

-