Browse all 255 reported symptoms of long COVID
Our ability to respond to environmental stimuli, such as taste and smell, suggests the necessity for a highly sensitive mechanism. G protein-coupled receptors (GPCRs) play an important role in these activities. They also control our emotions, behavior, and immune system. As a result, it is understandable that the hub genes found for all of the collective symptoms included in our study are related to GPCRs. They are GNGT1, GNG12, GNB3, GNB4, GNG13, GNG8, GNG3, GNG7, GNG10, and GNAI1. GPCRs’ adaptability to changing environmental conditions is based on their ability to bind varied ligands, change conformation, up- or down-regulate membrane expression, and interact with other proteins and receptors to form homo- or heterodimers. As a result, GPCRs interact with a wide variety of extracellular and intracellular proteins, including signaling molecules and other membrane proteins. Around half of the more than 800 human GPCRs have sensory functions that govern olfaction, light perception, and pheromone signaling.
More than 90% of the remainder of non-sensory GPCRs, which number over 370, are expressed in the brain and mediate communication from many types of ligands, regulating several physiological processes throughout the human organism, primarily endocrine and neurological activities. GPCRs are the most commonly used therapeutic medication targets.
At the subcellular level, Gi/o-coupled GPCRs can be detected and analyzed for functions such as neurite outgrowth, neurotransmitter release, and synaptic plasticity, which are then processed into complex brain processes like as memory, learning, and cognition. Short and long-term memory, memory consolidation, and learning are all mediated by serotonin, dopamine, cannabinoid, and metabotropic glutamate receptors. Most GPCRs, including dopamine, serotonin, and opioid receptors, play an important role in modifying and affecting behavior and emotions. GPCR signaling is also important in the control of sleep and the circadian rhythm.
In addition, we investigated the pathways, biological processes, molecular functions, and cellular components with the highest occurrences of all symptoms.
KEGG pathway
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | GABAergic synapse | 1.803e-24 | 5.585e-23 | 199110.00 | 10885805.27 |
| 2 | Morphine addiction | 2.279e-24 | 5.585e-23 | 199090.00 | 10838083.83 |
| 3 | Circadian entrainment | 4.461e-24 | 7.286e-23 | 199030.00 | 10701194.73 |
| 4 | Serotonergic synapse | 2.202e-23 | 1.972e-22 | 198870.00 | 10375033.46 |
| 5 | Cholinergic synapse | 2.202e-23 | 1.972e-22 | 198870.00 | 10375033.46 |
GO: Biological Process
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | positive regulation of protein localization to cell cortex (GO:1904778) | 0.002498 | 0.02591 | 555.17 | 3326.77 |
| 2 | regulation of triglyceride metabolic process (GO:0090207) | 0.002498 | 0.02591 | 555.17 | 3326.77 |
| 3 | regulation of hormone metabolic process (GO:0032350) | 0.002498 | 0.02591 | 555.17 | 3326.77 |
| 4 | regulation of protein localization to cell cortex (GO:1904776) | 0.003994 | 0.02591 | 317.19 | 1751.86 |
| 5 | response to forskolin (GO:1904321) | 0.004492 | 0.02591 | 277.53 | 1500.17 |
GO: Molecular function
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | GTPase activity (GO:0003924) | 2.998e-10 | 3.598e-9 | 141.29 | 3098.09 |
| 2 | G protein-coupled serotonin receptor binding (GO:0031821) | 0.002997 | 0.01199 | 444.11 | 2580.41 |
| 3 | nucleoside-triphosphatase activity (GO:0017111) | 1.370e-9 | 8.218e-9 | 108.74 | 2219.23 |
| 4 | PDZ domain binding (GO:0030165) | 0.03106 | 0.07922 | 35.71 | 123.99 |
| 5 | GDP binding (GO:0019003) | 0.03301 | 0.07922 | 33.54 | 114.41 |
GO: Cellular Component
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | heterotrimeric G-protein complex (GO:0005834) | 2.731e-25 | 1.366e-24 | 7487.25 | 423477.90 |
| 2 | cell cortex region (GO:0099738) | 0.005488 | 0.01241 | 222.00 | 1155.57 |
| 3 | lytic vacuole membrane (GO:0098852) | 0.007445 | 0.01241 | 18.61 | 91.19 |
| 4 | lysosomal membrane (GO:0005765) | 0.01119 | 0.01399 | 14.99 | 67.33 |
| 5 | lysosome (GO:0005764) | 0.02250 | 0.02250 | 10.27 | 38.97 |
Hub genes as predicted biomarker & predicted FDA approved drugs
| Hub Genes (ranked) | FDA-Approved Drugs |
| GNGT1 | – |
| GNG12 | – |
| GNB3 | CLONIDINE, SILDENAFIL, TORSEMIDE, NORTRIPTYLINE |
| GNB4 | – |
| GNG13 | – |
| GNG8 | – |
| GNG3 | – |
| GNG7 | – |
| GNG10 | – |
| GNAI1 | – |
