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Viruses 2018, 10(6), 283; https://doi.org/10.3390/v10060283

Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro

1
Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea
2
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
3
Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Korea
4
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
The authors contributed equally to this article.
*
Author to whom correspondence should be addressed.
Received: 5 April 2018 / Revised: 15 May 2018 / Accepted: 21 May 2018 / Published: 24 May 2018
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

The Middle East respiratory syndrome-coronavirus (MERS-CoV), first identified in Saudi Arabia, is an emerging zoonotic pathogen that causes severe acute respiratory illness in humans with a high fatality rate. Since its emergence, MERS-CoV continues to spread to countries outside of the Arabian Peninsula and gives rise to sporadic human infections following the entry of infected individuals to other countries, which can precipitate outbreaks similar to the one that occurred in South Korea in 2015. Current therapeutics against MERS-CoV infection have primarily been adapted from previous drugs used for the treatment of severe acute respiratory syndrome. In search of new potential drug candidates, we screened a library composed of 2334 clinically approved drugs and pharmacologically active compounds. The drug saracatinib, a potent inhibitor of Src-family of tyrosine kinases (SFK), was identified as an inhibitor of MERS-CoV replication in vitro. Our results suggest that saracatinib potently inhibits MERS-CoV at the early stages of the viral life cycle in Huh-7 cells, possibly through the suppression of SFK signaling pathways. Furthermore, saracatinib exhibited a synergistic effect with gemcitabine, an anticancer drug with antiviral activity against several RNA viruses. These data indicate that saracatinib alone or in combination with gemcitabine can provide a new therapeutic option for the treatment of MERS-CoV infection. View Full-Text
Keywords: Middle East Respiratory Syndrome; MERS-CoV; Src-family kinase inhibitor; saracatinib; gemcitabine Middle East Respiratory Syndrome; MERS-CoV; Src-family kinase inhibitor; saracatinib; gemcitabine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Shin, J.S.; Jung, E.; Kim, M.; Baric, R.S.; Go, Y.Y. Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro. Viruses 2018, 10, 283.

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