Supercomputer Model Identifies Pathways and Possible Weaknesses of COVID-19

Oak Ridge National Laboratory supercomputer modeling analysis suggests COVID-19 causes the inflammatory molecule bradykinin to run amuck in the human body. The Bradykinin storm cause gel to form in the lungs and the blood vessels to leak. The same analysis identifies about ten interventions to reduce the severity of COVID-19. An easy precaution is to take some Vitamin D. This will not prevent COVID-19 but might help reduce the chance for a severe case and reduce the severity of it.

Michael R Garvin, Christiane Alvarez, J Izaak Miller, Erica T Prates, Angelica M Walker, B Kirtley Amos, Alan E Mast, Amy Justice, Bruce Aronow wrote the researchELife – A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm

The data shows COVID-19 increases production of hyaluronic acid (HLA) in the lungs. HLA is often used in soaps and lotions for its ability to absorb more than 1,000 times its weight in fluid. When it combines with fluid leaking into the lungs, the results are disastrous: It forms a hydrogel, which can fill the lungs in some patients. This becomes like trying to breathe through Jell-O.

The renin–angiotensin system (RAS) controls many aspects of the circulatory system, including the body’s levels of a chemical called bradykinin, which normally helps to regulate blood pressure. According to the team’s analysis, when the virus tweaks the RAS, it causes the body’s mechanisms for regulating bradykinin to go haywire. Bradykinin receptors are resensitized, and the body also stops effectively breaking down bradykinin.

The bradykinin hypothesis provides a model that provides a better understanding COVID-19. It predicts nearly all the disease’s symptoms, even bruises on the toes that at first appear random.

Potential interventions
Several interventional points (most of them already FDA-approved pharmaceuticals) could be explored with the goal of increasing ACE, decreasing BK, or blocking BK2 receptors.

Several drugs target aspects of the RAS and are already FDA approved to treat other conditions. They could be applied to treating Covid-19 as well. Danazol, stanozolol, and ecallantide reduce bradykinin production and could potentially stop a deadly bradykinin storm.

Icatibant reduces bradykinin signaling and could blunt its effects once it’s already in the body.

Vitamin D is a potentially useful Covid-19 drug. It could stop potentially deadly bradykinin storms from forming. Vitamin D has already been shown to help those with Covid-19. Around 20% of the US population is Vitamin D deficient. This is a relatively safe way to reduce the severity of the virus.

Other compounds could treat symptoms associated with bradykinin storms. Hymecromone, for example, could reduce hyaluronic acid levels, potentially stopping deadly hydrogels from forming in the lungs. And timbetasin could mimic the mechanism that the researchers believe protects women from more severe Covid-19 infections. The potential treatments will need to be studied in a rigorous, controlled environment before their effectiveness could be determined and they could be used more broadly.

Functionally annotated network of genes involved in the hypertension-hypotension axis whose expression across the GTEx population is correlated and anticorrelated with the AGTR1 and AGTR2 receptors.

Critically disrupted RAS and Bradykinin pathways in COVID-19 BAL samples.

SOURCES- Oak Ridge National Lab, E-life, The Scientist, Medium
Written By Brian Wang,