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
. 2013 Dec;67(6):606-16.
doi: 10.1016/j.jinf.2013.09.029. Epub 2013 Oct 3.

Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus

Jasper F W Chan  1 , Kwok-Hung Chan, Richard Y T Kao, Kelvin K W To, Bo-Jian Zheng, Clara P Y Li, Patrick T W Li, Jun Dai, Florence K Y Mok, Honglin Chen, Frederick G Hayden, Kwok-Yung Yuen
Affiliations

Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus

Jasper F W Chan et al. J Infect. 2013 Dec.

Abstract

Objectives: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged to cause fatal infections in patients in the Middle East and traveler-associated secondary cases in Europe and Africa. Person-to-person transmission is evident in outbreaks involving household and hospital contacts. Effective antivirals are urgently needed.

Methods: We used small compound-based forward chemical genetics to screen a chemical library of 1280 known drugs against influenza A virus in Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of the identified compounds and of interferons, nelfinavir, and lopinavir because of their reported anti-coronavirus activities in terms of cytopathic effect inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level-3 laboratory.

Results: Ten compounds were identified as primary hits in high-throughput screening. Only mycophenolic acid exhibited low EC50 and high selectivity index. Additionally, ribavirin and interferons also exhibited in-vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic doses of mycophenolic acid and interferon-β1b were 60-300 and 3-4 times higher than the concentrations at which in-vitro anti-MERS-CoV activities were demonstrated, whereas that of ribavirin was ∼2 times lower. Combination of mycophenolic acid and interferon-β1b lowered the EC50 of each drug by 1-3 times.

Conclusions: Interferon-β1b with mycophenolic acid should be considered in treatment trials of MERS.

Keywords: Antiviral; Coronavirus; Interferon; Middle East; Mycophenolic acid; Ribavirin.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Viral load quantified by RT-PCR in Vero cells on day 3 after infection by MERS-CoV and inoculation with different drug compounds: (a) mycophenolic acid, (b) ribavirin, (c) interferons (Intron A, Avonex, Rebif, and Betaferon).
Figure 2
Figure 2
Photos of plaque reduction assay of mycophenolic acid, ribavirin, and Betaferon.
Figure 3
Figure 3
Effects of (a) mycophenolic acid, (b) ribavirin, and (c) interferons (Intron A, Avonex, Rebif, and Betaferon) on MERS-CoV replication in Vero cells.
See this image and copyright information in PMC

References

    1. Chan J.F., Li K.S., To K.K., Cheng V.C., Chen H., Yuen K.Y. Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J Infect. 2012;65:477–489. - PMC - PubMed
    1. Chan J.F., Lau S.K., Woo P.C. The emerging novel Middle East respiratory syndrome coronavirus: the “knowns” and “unknowns”. J Formos Med Assoc. 2013;112:372–381. - PMC - PubMed
    1. Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814–1820. - PubMed
    1. de Groot R.J., Baker S.C., Baric R.S., Brown C.S., Drosten C., Enjuanes L. Middle East respiratory syndrome coronavirus (MERS-CoV); announcement of the coronavirus study group. J Virol. 2013;87:7790–7792. - PMC - PubMed
    1. World Health Organization . WHO; Geneva: 2013. Global alert and response: Middle East respiratory syndrome coronavirus (MERS-CoV) – update – as of 4 October 2013.http://www.who.int/csr/don/2013_10_04/en/index.html [accessed 05.10.13]

Publication types

MeSH terms