Class A Orphans (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database

Abstract

CoronavirusesCoronaviruses are large, often spherical, enveloped, single-stranded positive-sense RNA viruses, ranging in size from 80-220 nm. Of the four structural proteins encoded in the viral genome, the RNA winds around the highly basic nucleocapsid (N) protein. The three other structural proteins, envelope (E), membrane (M) and spike (S), are transmembrane proteins. The E protein is a small (9-12 kDa) single transmembrane domain protein, which enables virus assembly with the M protein, a larger (23-35 kDa) 3TM protein. Coronaviruses are named for the crown-shaped appearance of the virus due to the large (120+ kDa) S spike 1TM glycoprotein, which forms extended homotrimers. The spike protein binds to the animal host cell by interacting with specific anchoring proteins, typically proteinases, such as angiotensin-converting enzyme 2 or aminopeptidase N. This binding facilitates viral entry into the cell and the release of the genome. Aside from the four structural proteins, the remainder of the genome encodes accessory or non-structural proteins and includes proteinases to cleave the two encoded polyproteins. The remainder of the genome encodes elements for viral replication, assembly and release, as well as proteins which manipulate the host's innate immune system.

Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice

“…The orphan G protein coupled receptor GPR19 is obligatory for adropin activity 21 , 24 , 25 and is also highly expressed in the CNS relative to other tissues 35 , 36 . High GPR19 expression in the embryonic brain suggests a role in development 37 . However, evidence for coupling of adropin with GPR19 is controversial 38 .…”

Protective Effect of Genistein against Compound 48/80 Induced Anaphylactoid Shock via Inhibiting MAS Related G Protein-Coupled Receptor X2 (MRGPRX2)

“…Human MRGPRX2 or its mouse orthologue MRGPRB2 is a Class A orphan GPCR expressed on primate's mast cells [16]. In a recent report in 2019 by IUPHAR/BPS, MRGPRX2 is listed as a Class A orphan GPCR for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to disease [17]. Now, it is known that direct activation of MRGPRX2 causes anaphylactoid shock in humans [1,18].…”

Establishing an Analogue Based In Silico Pipeline in the Pursuit of Novel Inhibitory Scaffolds against the SARS Coronavirus 2 Papain-Like Protease

“…To evaluate scaffold novelty, we used our four hits to screen 1474 molecules, and 8904 molecules, annotated with the keyword ‘SARS-CoV-2’ in PubChem ( ), and the ChemBL database [ 81 ] ( ), respectively, using DataWarrior’s, version 5.2.1 ( ) [ 82 ] default fingerprint descriptor FragFp, but found no hits. Likewise, we found no similar hits when we analysed the structures submitted to the COVID Moonshot Initiative [ 83 ] ( ), and IUPHAR/BPS Guide to Pharmacology [ 36 , 37 ] ( ). Additionally, the compounds’ PubChem Bioassay profiles were also checked.…”

“…The M pro has been the subject of intense scrutiny, with 23 investigational inhibitors of varying potency identified thus far [ 36 , 37 ]. Conversely, only one small-molecule inhibitor, GRL-0617, with experimental data has been reported for the SARS-CoV-2 PL pro , by the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society (IUPHAR/BPS) Guide to Pharmacology [ 36 , 37 ], with a half-maximal inhibitory concentration (IC 50 ) of 2.4 µM [ 38 ]. Ebselen has also been presented as a potential inhibitor of PL pro in a pre-print article [ 39 ].…”