The following will be a long evolving thread of previously selected genes with high similarity to SARS-Cov2. And its possible involvement in long covid. But some disclaimers. #COVID19 #LongCovid

This is not medical advice, it's just an effort to broaden the discussion regarding post-acute sequelae and long covid. I have a substack on which I describe other methods to analyze genomic data. #COVID19 #LongCovid
https://tavoglc.substack.com/

Posts data and code are free and open source, feel free to subscribe if you think the following can be useful. Supporting this project will allow me to continue to work on these analyses. #COVID19 #LongCovid

Due to its seasonality(solar radiation changes), I think that one of the main dysregulations is the circadian one. Scheduling of circadian events could be disrupted and some daily variations in symptom severity might also be possible. #COVID19 #LongCovid

One of the main regulators of the circadian function inside cells is the CLOCK protein, a gen with high compositional similarity to SARS-Cov. CLOCK is involved in chromatin organization and the circadian cycle. #COVID19 #LongCovid
https://www.genecards.org/cgi-bin/carddisp.pl?gene=CLOCK

Delayed sleep phase disorder(DSPD) and Major depressive disorder are diseases associated with CLOCK. DSPD disrupts the timing of biological rhythms such as sleep, periods of alertness, body temperature, and hormonal cycles. #COVID19 #LongC
https://en.wikipedia.org/wiki/Delayed_sleep_phase_disorder

Involvement between SARS Cov2 and the circadian rhythm has been proposed before. #COVID19 #LongC
https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.949

Specific molecular machinery involved in circadian regulation and highjacked by SARSCov2 infection has already been found. BMAL1, a protein that interacts with CLOCK to synchronize the circadian rhythm, regulates the entry of the virus into the cell. #COVID19 #LongC
https://www.sciencedirect.com/science/article/pii/S2589004221011123

And either pharmacological or genetic targeting of BMAL1 reduces SARSCov2 replication. #COVID19 #LongCovid

Pharmacological interventions targeting CLOCK have also been successful in COVID-19 treatment. Lithium an inducer of clock gene expression has shown inhibitory effects of SARS Cov2 replication at the preclinical level. #COVID19 #LongCovid
https://www.sciencedirect.com/science/article/pii/S075333222200261X

As well as a faster recovery rate, lowering the days with lymphopenia in a randomized clinical trial setting. #COVID19 #LongCovid
https://www.frontiersin.org/articles/10.3389/fphar.2022.850583/full

Also, electronic health records showed a lower incidence of COVID-19 cases in subjects with therapeutic levels of lithium in their blood. #COVID19 #LongCovid
https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/abs/association-between-serum-lithium-level-and-incidence-of-covid19-infection/C10A4E115ECCB30AA8FAC30220D1E240

Treating long covid is harder to assess, but there is at least one clinical trial assessing the efficacy with what appears to be promising results. #COVID19 #LongC
https://buffalohealthyliving.com/long-covid-symptoms-low-dose-lithium-may-help-call-716-829-5454/

For some reason, I forgot to add the list of selected genes. This one contains the RefSeq Id #COVID19 #LongCovid

https://github.com/TavoGLC/SARSCov2Solar/blob/main/data/fold_out_0.txt

And this one contains the gene description from the refseq file.

https://github.com/TavoGLC/SARSCov2Solar/blob/main/data/fold_out_names0.txt

Another common symptom of long covid is exercise intolerance. Although it is an uncommon symptom many other diseases generate exercise intolerance. One of those is Catecholaminergic polymorphic ventricular tachycardia (CPVT). #COVID19 #LongCovid
https://en.wikipedia.org/wiki/Catecholaminergic_polymorphic_ventricular_tachycardia

CPVT causes an abnormal heart rate (arrhythmia) that can be fatal and is triggered by conditions of high excitement such as physical exercise. Mutations in Calmodulin 2, a calcium-handling protein, lead to CPVT. #COVID19 #LongCovid
https://pubmed.ncbi.nlm.nih.gov/25557436/

Calmodulin 2 is also associated with a series of cardiac diseases and Sudden Infant Death Syndrome. The main mechanism behind this is due to lower calcium affinity impairing calcium signaling. #COVID19 #LongCovid
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0153851

Calmodulin 2 is also another protein with high compositional similarity to SARSCov2 and also has a role inside the SARSCov2 infection pathway. Calmodulin interaction with ACE2 is important for the infection process. #COVID19 #LongCovid
https://link.springer.com/article/10.1007/s00228-020-02963-4

Glycogen storage disease is also another exercise-intolerant disease. Particularly GSD III involves the liver, skeletal, and heart muscle, one cause of such disease is a mutation in the AGL gene. #Covid #LongCovid
https://www.ncbi.nlm.nih.gov/books/NBK26372/

The AGL gene is a gene with high similarity to the SARS Cov2 genome and codifies for the AGL protein, a protein that debranches glycogen. Exercise intolerance in the scheme of GSD III has been suggested to be an energy deficiency. #Covid #LongCovid
https://pubmed.ncbi.nlm.nih.gov/23507172/

Direct involvement of AGL with SARSCov2 infection has not been found, however pharmacological treatments aiming at AGL have been found to inhibit viral replication. #Covid #LongCovid
https://academic.oup.com/glycob/article/31/4/378/5911971?login=false

While Duvoglustat, another molecule that targets AGL only has been proposed as a treatment for viral infections. #Covid #LongCovid
https://pubs.acs.org/doi/full/10.1021/acs.jnatprod.0c00968

Another glycogen disease is Fanconi-Bickel Syndrome, among the main symptoms of this disease are myalgia, muscle cramp, and muscle rigidity. A gene associated with this disease is the SLC2A2 also known as GLUT2, a gene with high similarity to the SARSCov2 genome. #COVID #LongCovid
https://www.malacards.org/card/fanconi_bickel_syndrome

GLUT2 is also associated with type 2 diabetes, a condition with a rising number of cases and COVID-19 infection increases the chances of developing the disease. #COVID #LongCovid
https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00044-4/fulltext

Specific dysregulation of GLUT2 due to SARSCov2 infection results in altered expression patterns of GLUT2 in the pancreas, altering its function. #COVID #LongCovid
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037197/

It has also been suggested as a possible target for dysregulation by SARSCov2 infection in the intestine leading to diarrhea. #COVID #LongCovid
https://journals.physiology.org/doi/full/10.1152/ajpgi.00021.2023

Treatment targeting GLUT2 has not been used to treat SARSCov2 infection or long covid. However, the diabetes treatment metformin has been used to treat infection with successful results for patients with type 2 diabetes. #COVID #LongCovid
https://www.nature.com/articles/s41598-022-09639-2

Regarding Long Covid metformin has been tested in a clinical trial with positive outcomes. However, the authors acknowledge the limitation of a lack of established criteria to define long covid. #COVID #LongCovid
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810227/

Metabolic alterations have been present in a series of genes, particularly involving diabetes. This suggests the highjacking of the insulin pathway from the virus, a component of this pathway is the PIK3C3 protein and its gene that is highly similar to the SARS Cov2 genome. #COVID #LongCovid
https://www.genecards.org/cgi-bin/carddisp.pl?gene=PIK3C3

One of the diseases in which PIK3C3 has been involved is Neurodegeneration with Brain Iron Accumulation (NBIA) "disorder characterized by an abnormal accumulation of iron in the brain and progressive degeneration of the nervous system" #COVID #LongCovid
https://www.malacards.org/card/neurodegeneration_with_brain_iron_accumulation

Iron accumulation has been suggested as a consequence of covid-19 by multiple studies. #COVID #LongCovid
https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.066865

However, a direct measurement of iron accumulation in the brain remains to be assessed. #COVID #LongCovid
https://www.degruyter.com/document/doi/10.1515/nipt-2022-0016/html

PIK3C3 has been involved in the early steps of viral infection, particularly due to its involvement in endosome recycling. #COVID #LongCovid
https://www.sciencedirect.com/science/article/pii/S0092867420313945#sec4

Multiple studies have shown that PIK3 inhibitors inhibit SARS Cov2 viral replication in cell culture. #COVID #LongCovid
https://www.nature.com/articles/s41588-021-00805-2

Exvivo analysis showed that inhibitors of PIK3 inhibited SARS Cov2 infection in ex vivo lung tissue cultures. #COVID #LongCovid
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26583

Clinically PIK3 inhibitors have shown decreased rates of COVID-19 in cancer patients. #COVID #LongCovid
https://jamanetwork.com/journals/jamaoncology/article-abstract/2783284

Quercetin, another PIK3 inhibitor has also shown faster recovery rates when used with antiviral drugs in a clinical trial setting. #COVID #LongCovid
https://www.sciencedirect.com/science/article/pii/S0014299921007718

@tavoglc Just as an aside, unrelated to your topic: You know you can type longer messages here? Having a chain of short messages isn't really comfortable to read. And yes, people will see the full posts, it's not like they get cut off or anything.