Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Infection with SARS coronavirus (SARS-CoV) induces a cellular stress condition known as the unfolded protein response (UPR). UPR induction is mediated primarily by viral spike (S) protein. The modulation of UPR by S protein involves activation of PERK protein kinase. Other branches of the UPR pathways controlled by IRE1 and ATF6 proteins, respectively, are not involved. 2. The protease inhibitor Ben-HCl effectively suppresses SARS-CoV infection by blocking virus entry. Viral infectivity is associated with the cleavage of S protein by the cellular protease factor Xa. 3. Two new aspects of the interaction between SARS-CoV S protein and the cell have been defined. These have important implications in the pathogenesis of SARS, providing opportunities for developing vaccines and antivirals against SARS-CoV. 4. Counteracting the UPR and targeting the cleavage of S protein with small molecule pharmaceutical agents represent two new anti-SARS-CoV strategies. 5. The receptor-binding domain of S protein delivered via adeno-associated virus can efficiently induce mucosal immunity and provide long-term protection against SARS-CoV infection.
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PMID:Roles of spike protein in the pathogenesis of SARS coronavirus. 1925 33

The 8ab protein of SARS-CoV is a group-specific accessory protein, which is lost when the virus was transmitted from animals to humans due to a 29-nucleotide deletion in the ORF8ab region. Here we found that 8ab protein is associated with ER membrane at luminal surface. 8ab protein was found to up-regulate the synthesis of endogenous ER-resident chaperons involved in protein folding through the activation of the transcription factor ATF6, while it showed no effect on the CHOP induction and XBP1 splicing associated with the unfolded protein response (UPR). When ectopically expressed in mammalian cells, 8ab induced the proteolysis of ATF6 and the translocation of its cleaved DNA-binding and transcription-activation domains from the ER to the nucleus. Finally, we showed that 8ab binds to the luminal domain of ATF6. These findings suggest that 8ab could modulate the UPR by activating ATF6 to facilitate protein folding and processing. Thus, the loss of 8ab in SARS-CoV through viral evolution in animals may play a role in its pathogenicity.
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PMID:The 8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces the activation of ATF6. 1930 6