LitCovid-sentences  

PMC:7293470 / 3409-6113 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T17 0-180 Sentence denotes We are developing a second generation bifunctional drug called DRhQ that can simultaneously bind to and inhibit both the TCR and CD74 through distinct regions of the construct [6].
T18 181-409 Sentence denotes DRhQ is comprised of the HLA-DRα1 domain with an L50Q amino acid substitution (to enhance binding affinity for CD74) linked to an autoantigen peptide (myelin oligodendroglial cell glycoprotein, i.e. MOG-35-55 peptide) (Fig. 1 ).
T19 410-637 Sentence denotes DRhQ was derived from soluble MHC Class II α1-β1-antigenic peptide constructs originally designed to ligate specific T cell receptors as the distal components of the trimolecular complex (called Recombinant TCR ligands – RTLs).
T20 638-957 Sentence denotes As partial TCR agonists these constructs, containing various disease-associated MHC and antigenic peptide components, could indeed inhibit MHC-restricted antigen specific T cells, but translation of RTL1000 for human use in a Phase 1 clinical trial (showing safety and tolerability) required MHC-matched recipients [7].
T21 958-1247 Sentence denotes Thus, the simpler DRhQ construct was designed, retaining just the conserved-in-human DRα1 domain (without the polymorphic HLA-DRβ1 domain) linked to the MOG-35-55 peptide extension, with the added benefit that it can be administered to all recipients without need for tissue type matching.
T22 1248-1461 Sentence denotes This has enabled use of the DRα1-MOG-35-55 construct to reverse ongoing neuroinflammation and disease signs in animal models of multiple sclerosis, stroke, methamphetamine disorders and traumatic brain injury [8].
T23 1462-1813 Sentence denotes These and other studies ([9], [10], [11] & unpublished data) revealed down-regulation of multiple proinflammatory components driven by both innate and adaptive immune responses that also contribute to the SARS-CoV-2 cytokine storm, including complement receptor C5aR1, platelet activation, IL-1β, IL-2, IL-6, TNF-α, CCR2 (receptor for CCL2) and CXCR2.
T24 1814-2101 Sentence denotes Of further importance, a partial HLA-DP RTL construct could inhibit activated pleural T cell infiltrates from patients with beryllium-induced lung fibroma [12], suggesting more-directly-relevant activity that could be potentially beneficial as a treatment of COVID-19 patients with ARDS.
T25 2102-2193 Sentence denotes Fig. 1 Dual activities of DRhQ that could block the “Cytokine Storm” induced by SARS-CoV-2.
T26 2194-2344 Sentence denotes DRhQ is a bifunctional drug comprised of the HLA-DRα1 domain covalently linked to human myelin oligodendroglial cell glycoprotein (MOG)-35-55 peptide.
T27 2345-2604 Sentence denotes Due to its unique design, DRhQ can bind to and inhibit both T cell receptors and the MHC “invariant” chain, CD74, that serves as the receptor for the proinflammatory homologs, MIF and MIF2, resulting in blockade of multiple contributors to the Cytokine Storm.
T28 2605-2616 Sentence denotes DRhQ image:
T29 2617-2704 Sentence denotes Green = DRα1L50Q domain; Dark green line = linker; Black = MOG-35-55 peptide extension.