Viruses. 2018 May 24;10(6). pii: E283. doi: 10.3390/v10060283.
Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro.
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.
KEYWORDS:
MERS-CoV; Middle East Respiratory Syndrome; Src-family kinase inhibitor; gemcitabine; saracatinib- PMID:
- 29795047
- PMCID:
- PMC6024778
- DOI:
- 10.3390/v10060283
- [Indexed for MEDLINE]
https://www.researchgate.net/figure/nhibition-of-MERS-CoV-infection-by-kinase-inhibitors-Kinase-inhibitors-were-added-either_fig4_269413261
(investigational status: saracatinib
https://en.wikipedia.org/wiki/Saracatinib
(investigational status: saracatinib
https://en.wikipedia.org/wiki/Saracatinib
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