Target Information
| Target General Information | Top | |||||
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| Target ID |
T97747
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| Target Name |
HUMAN C-C chemokine receptor 5 (CCR5)
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| Synonyms |
HIV-1 fusion coreceptor; HIV-1 fusion co-receptor; Chemokine receptor CCR5; CMKBR5; CHEMR13; CD195 antigen; CD195; CCR-5; CC-CKR-5; C-C CKR-5
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| Gene Name |
CCR5
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | COVID-19 [ICD-11: 1D6Y] | |||||
| Function |
May play a role in the control of granulocytic lineage proliferation or differentiation. Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Drugs in Phase 2 Trial | [+] 1 | + | ||||
| 1 | Leronlimab | Drug Info | Phase 2 | Coronavirus Disease 2019 (COVID-19) | [2], [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Leronlimab | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Maraviroc | Ligand Info | |||||
| Structure Description | Crystal Structure of the CCR5 Chemokine Receptor | PDB:4MBS | ||||
| Method | X-ray diffraction | Resolution | 2.71 Å | Mutation | Yes | [4] |
| PDB Sequence |
PCQKINVKQI
28 AARLLPPLYS38 LVFIFGFVGN48 MLVILILINY58 KRLKSMTDIY68 LLNLAISDLF 78 FLLTVPFWAH88 YAAAQWDFGN98 TMCQLLTGLY108 FIGFFSGIFF118 IILLTIDRYL 128 AVVHAVFALK138 ARTVTFGVVT148 SVITWVVAVF158 ASLPNIIFTR168 SQKEGLHYTC 178 SSHFPYSQYQ188 FWKNFQTLKI198 VILGLVLPLL208 VMVICYSGIL218 KTLLRMKKYT 1005 CTVCGYIYNP1015 EDGDPDNGVN1025 PGTDFKDIPD1035 DWVCPLCGVG1045 KDQFEEVEEE 227 KKRHRDVRLI237 FTIMIVYFLF247 WAPYNIVLLL257 NTFQEFFGLN267 NCSSSNRLDQ 277 AMQVTETLGM287 THCCINPIIY297 AFVGEEFRNY307 LLVFFQ
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TYR37
3.106
TRP86
3.510
TYR89
3.642
THR105
4.641
TYR108
3.619
PHE109
3.482
PHE112
3.714
PHE182
3.206
LYS191
3.757
GLN194
3.837
THR195
3.291
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| Ligand Name: Oleic acid | Ligand Info | |||||
| Structure Description | Crystal Structure of CC Chemokine Receptor 5 (CCR5) in complex with high potency HIV entry inhibitor 5P7-CCL5 | PDB:5UIW | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [5] |
| PDB Sequence |
TSEPCQKINV
25 KQIAARLLPP35 LYSLVFIFGF45 VGNMLVILIL55 INYKRLKSMT65 DIYLLNLAIS 75 DLFFLLTVPF85 WAHYAAAQWD95 FGNTMCQLLT105 GLYFIGFFSG115 IFFIILLTID 125 RYLAVVHAVF135 ALKARTVTFG145 VVTSVITWVV155 AVFASLPNII165 FTRSQKEGLH 175 YTCSSHFPYS185 QYQFWKNFQT195 LKIVILGLVL205 PLLVMVICYS215 GILKTLLRMK 1002 KYTCTVCGYI1012 YNPEDGDPDN1022 GVNPGTDFKD1032 IPDDWVCPLC1042 GVGKDQFEEV 1052 EEEKKRHRDV234 RLIFTIMIVY244 FLFWAPYNIV254 LLLNTFQEFF264 GLNNCSSSNR 274 LDQAMQVTET284 LGMTHCCINP294 IIYAFVGEEF304 RNYLLVFFQK314 HI |
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Viral life cycle - HIV-1 | hsa03250 | Affiliated Target |
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| Class: Genetic Information Processing => Information processing in viruses | Pathway Hierarchy | ||
| Virion - Human immunodeficiency virus | hsa03260 | Affiliated Target |
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| Class: Genetic Information Processing => Information processing in viruses | Pathway Hierarchy | ||
| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Viral protein interaction with cytokine and cytokine receptor | hsa04061 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Chemokine signaling pathway | hsa04062 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Endocytosis | hsa04144 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 17 | Degree centrality | 1.83E-03 | Betweenness centrality | 6.23E-04 |
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| Closeness centrality | 2.15E-01 | Radiality | 1.38E+01 | Clustering coefficient | 1.54E-01 |
| Neighborhood connectivity | 2.11E+01 | Topological coefficient | 1.00E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Disruption of the CCL5/RANTES-CCR5 Pathway Restores Immune Homeostasis and Reduces Plasma Viral Load in Critical COVID-19 | |||||
| REF 2 | ClinicalTrials.gov (NCT04343651) Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate COVID-19 | |||||
| REF 3 | Leronlimab Shows Further Promise for COVID-19 Treatment, Study Shows. May 09, 2020 | |||||
| REF 4 | Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex. Science. 2013 Sep 20;341(6152):1387-90. | |||||
| REF 5 | Structure of CC Chemokine Receptor 5 with a Potent Chemokine Antagonist Reveals Mechanisms of Chemokine Recognition and Molecular Mimicry by HIV. Immunity. 2017 Jun 20;46(6):1005-1017.e5. | |||||
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