Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Enjuanes, Luis
Location Spanish National Research Council (CSIC)
Primary Field Animal, Nutritional and Applied Microbial Sciences
 Research Interests
Enjuanes group engineered the first infectious coronavirus cDNA clone using bacterial artificial chromosomes, which facilitated studies of virus replication and pathogenesis. They identified key viral and cellular proteins that interact with coronavirus RNA and are critical for virus replication. They made major contributions to understanding how short distance and long-distance RNA interactions were required for optimal coronavirus RNA transcription and replication. Enjuanes team was the first to show how a single small membrane protein (E) was critical for virus assembly, and regulated cell stress and the unfolded protein response. E protein was a virulence factor including a PDZ binding motif (PBM) at the carboxy-terminus of the three deadly human CoVs. This PBM binds a cellular protein (syntenin) activating p38 MAPK and leading to lung inflammation, edema, and mice death. Inhibitors of this signaling pathway significantly increased mice survival after infection with SARS-CoV. A second virulence factor described by Enjuanes team, the ion channel activity encoded in SARS-CoV E protein, regulates Ca++ transportation activating inflammasome and leading to lung edema. Enjuanes group has developed MERS-CoV and SARS-CoV-2 vaccine candidates, based on replication-competent propagation-defective RNA replicons RNA replicons providing sterilizing immunity. These vaccines are delivered in two formats: chemically defined, composed of the RNA replicon and nanoparticles, or on propagation deficient virus-like particles (VLPs). These replicons induce sterilizing immunity in mice models. ~ ~

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