A Comprehensive Bioinformatics Study
Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is a chronic condition with lingering symptoms such as fatigue, neurological impairments, and respiratory issues. Current treatment options are limited. This study explores the role of GPCRs, a major class of druggable cell-surface receptors, as potential therapeutic targets. The project integrates multiple bioinformatics approaches to:
- Identify GPCRs associated with long COVID genes
- Analyze sequence/function/network relationships
- Simulate molecular interactions
- Suggest possible FDA-approved or repurposed drugs
- Functional Mapping: Identify long COVID-related genes with GPCR involvement
- Network Analysis: Prioritize key GPCR targets using Cytoscape & STRING
- Docking Simulations: Perform ligand–receptor docking for interaction affinity
- Drug Repurposing: Highlight potential treatments from known drugs
Tool/Database | Purpose |
---|---|
ToppGene / DAVID | Functional enrichment, similarity analysis |
EMBOSS / BLAST | Sequence alignment and comparison |
STRING | Protein-protein interaction network generation |
Cytoscape + CytoHubba | Network ranking & hub identification |
PPA-Pred | Protein-protein affinity docking |
PyRx | Ligand-receptor docking simulation |
Swiss-Model / PDB | Structure modeling and retrieval |
UCSF Chimera | 3D visualization of structures |
DrugBank / PubChem | Drug annotation and repurposing info |
This study led to the identification of 21 GPCR-associated genes through functional enrichment, sequence alignment, protein-protein affinity prediction, and docking simulations. These genes were analyzed in connection to long COVID symptoms and their potential as therapeutic targets.
- HRAS, KRAS, GNAQ, and GNA11 were consistently identified across multiple analyses.
- These genes are involved in immune signaling, neurological processes, and cellular communication—core systems disrupted in Long COVID.
Gene | Associated Symptoms | Suggested Drugs |
---|---|---|
GNAQ | Venous thrombosis, pulmonary embolism | Verteporfin, Selumetinib |
GNA11 | Ocular pain, alopecia | Binimetinib, Cabozantinib, Selumetinib |
KRAS | Fatigue, GI issues, autoimmunity | Panitumumab, Cetuximab, Adagrasib, Sotorasib |
PRKACA | Memory impairment, mania, alopecia | (Limited repurposing data) |
- Additional promising candidates: Naltrexone, Tipifarnib
- Strong binding affinities (e.g., –9.6 kcal/mol for GNAQ–CAMKK1)
- RMSD values of 0.0 suggest highly stable receptor-ligand complexes
- High-confidence docking pairs:
- GNAQ – CAMKK1
- PRKACA – PRKACB
- CAMK2A – CAMK2B
- 12 of the 21 genes were mapped to Long COVID symptoms
- HRAS: Sleep apnea, reflux, alopecia
- KRAS: Fatigue, edema, abdominal pain
- PRKAR1A: Irregular menstruation, neuropsychiatric impairment
- Cytoscape MCC analysis ranked GNA11 and GNAQ as key hub genes
- Functional pathways enriched include:
- GPCR signaling
- Immune regulation
- Neurological pathways
- Genes like GNA15, GNAT3, PRKCA lack known symptom/drug links—suggesting novel research opportunities
This research project offers a comprehensive investigation into the therapeutic potential of G Protein-Coupled Receptors (GPCRs) in managing Long COVID. Through integrated computational approaches, it identified and prioritized 21 GPCR genes as potential therapeutic targets.
- GPCR genes including HRAS, KRAS, GNAQ, GNA11 were consistently highlighted
- Repurposed drugs such as Naltrexone, Tipifarnib, Sotorasib, and Cabozantinib showed strong therapeutic relevance
- The role of GPCRs in immune, neurological, and vascular systems underscores their importance in long COVID
- Reliance on in silico methods; experimental confirmation is pending
- Default parameter limitations may have excluded borderline results
- Correlation ≠ causation; findings are hypothesis-generating
- Experimental validation via in vitro/in vivo studies
- Biased ligand design for selective GPCR targeting
- Exploration of autoantibody neutralization strategies
- Incorporating patient-specific genetic data for personalized therapy
- Initiating clinical trials for top drug candidates
- Protein interaction networks
- Top docking poses and 3D binding visualizations
- Affinity score charts and heatmaps
All figures are available in the
/Figures/
directory.
Title: Exploring G-Protein Coupled Receptor (GPCR) as Therapeutic Application of Long COVID
Author: Dhanyashri A/P Guruparan
Institution: Management & Science University (MSU), Malaysia
Submitted: 2024
📄 Full Report: [manuscript_LongCovid_Therapeutics.pdf
]
- Browse the folders to explore materials by category (network, docking, simulation).
- Open any
.pdb
or.pdbqt
files in UCSF Chimera or PyRx to view 3D structures. - View CSV/Excel files in
Docking_PPA-Pred
orDocking_Simulation
for result summaries. - Use the README to understand the logic behind each experiment.
This project is licensed under the MIT License. For academic use only.
- Validation of docking predictions via wet-lab experiments
- Expansion to other receptor families (e.g., kinases)
- Multi-drug synergy simulations for combination therapy
| This work is original and solely belongs to the author (Dhanyashri) and MSU. All materials and results are intended for academic and non-commercial research purposes only.