1. University of Missouri and John Hopkins Medical School - https://www.uptodate.com/contents/pharmacology-of-mammalian-mechanistic-target-of-rapamycin-mtor-inhibitors

2. Albert Einstein College of Medicine - https://www.longevity.technology/covid-19-leading-clinician-calls-for-focus-on-the-biology-of-aging/


University of California, Santa Cruz

Rapamycin (sirolimus) is an FDA-approved immunosuppressant and mTOR inhibitor known for its immunosuppressive and antiproliferative properties, which are used to treat tuberous sclerosis, psoriasis, and certain malignancies. Because of these properties, researchers have investigated its potential to mitigate severe COVID-19, with some experts suggesting it could significantly reduce disease severity in elderly patients.

Rapamycin as a Treatment for COVID-19

This double-blinded study aims to find the virological efficacy of rapamycin in treating COVID-19.

Participants of this study will be COVID-19 patients placed in one of two groups. One group will be treated with standard medical care, in addition to a 10mg dose of sirolimus on day one and a 5mg dose of sirolimus on days two to seven. Patients in the second, or control, group will only be treated with standard medical care and placebo dosages for all seven days.


Clinical Study: Thomas Jefferson University (August 2020 Completion)

Conducted by the University of Cincinnati, this study aims to determine if sirolimus can improve clinical outcomes for patients with a severe case of COVID-19, particularly those simultaneously experiencing pneumonia. 

For each trial, thirty patients will be separated into three groups. With a 2:1 ratio, two groups will be given a 6mg of sirolimus on day one and 2mg of sirolimus on the next thirteen days or until hospital discharge (whichever comes first). The third group will be given placebo dosages. Observations will be recorded daily and specific biomarkers will be studied on day one, day three, day seven, and day fourteen.


Clinical Study: University of Cincinnati (September 2020 Completion)

Rapamycin is able to complete its functions by its ability to prevent cytokine signaling that promotes lymphocyte growth and differentiation. 

To do so, upon entering the cytoplasm, rapamycin binds to the FK binding protein, which monitors the activity of the mechanistic target of rapamycin (mTOR). Once activated, the mTOR inhibits interleukin (IL)-2-mediated signal transduction, which stops the cell cycle during the transition between the G1 and S phase. As a result, further bacterial cell-cycle progression and proliferation is prevented. 



Mode of Action

The immunosuppressive properties of rapamycin are primarily produced in two important steps/actions. 

Rapamycyn inhibits the p70 S6 kinase, which is activated upon the catalyzation of the substrate 40S ribosomal subunit S6 protein. By prevent the catalytic activity, rapamycin reduces the translation of certain mRNA, and as a result, decreases protein synthesis 
Rapamcin, consequently, binds to intracellular proteins, creating a complex that ultimately helps increase the efficiency of such immunosuppressants. 


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