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Emerging human coronaviruses: pathogenesis and protection
PRBB CRG Conferences
by Luis Enjuanes from CSIC
Host: Fátima Gebauer (CRG)

The World is facing a pandemic caused by the third deadly human coronavirus
(CoV) identified. This virus uses novel abilities to efficiently disseminate, like
remaining asymptomatic to avoid its identification, and been already activated
before been released from the cell where it is produced, providing strong
advantage to cause a variety of disease. There are several strategies to prevent
viral epidemics. Among them vaccine development is probably the most
efficient, followed by the development of antivirals. Our laboratory has focused
in coronavirus-host interactions, what provided key information for the
development of both strategies. Using a combination of chemical synthesis and
reverse genetics, we have engineered infectious cDNA for the three deadly
human CoVs (SARS-CoV-1, MERS-CoV, and SARS-CoV-2). Deletion of group
specific viral genes led to the identification of genes involved in virus virulence,
and the generation of attenuated viruses as vaccine candidates. From them
safe RNA replicons defective in propagation were engineered that provided full
protection against coronavirus infections. CoVs of genera , ,  and  encode
proteins that have a PDZ-binding motif (PBM), which may bind over 400 cellular
proteins containing PDZ domains, making them relevant for the control of cell
function. It was demonstrated that SARS-CoV E protein PBM binds to cellular
syntenin PDZ. This interaction activated p38MAPK, which induced an
exacerbated proinflammatory response leading to virus pathogenesis. In fact,
inhibition of p38MAPK lead to the survival of at least 80% of the infected mice,
confirming the relevance of this signaling pathway and leading to the
identification of potent antivirals for these CoVs.

Jul 13, 2020 12:00 PM in Madrid

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