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Challenges of rapamycin repurposing as a potential therapeutic candidate for COVID-19: implications for skeletal muscle metabolic health in older persons
Univ Toronto, Fac Kinesiol & Phys Educ, Dept Exercise Sci, Toronto, ON, Canada..ORCID iD: 0000-0003-1422-0154
Manchester Metropolitan Univ, Musculoskeletal Sci & Sports Med Res Ctr, Dept Sport & Exercise Sci, Manchester, Lancs, England..ORCID iD: 0000-0003-1330-4030
Univ Toronto, Fac Kinesiol & Phys Educ, Dept Exercise Sci, Toronto, ON, Canada..ORCID iD: 0000-0002-9367-1852
Univ Toronto, Fac Kinesiol & Phys Educ, Dept Exercise Sci, Toronto, ON, Canada..
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2022 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 322, no 6, p. E551-E555Article in journal (Refereed) Published
Abstract [en]

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that has spread worldwide, resulting in over 6 million deaths as of March 2022. Older people have been disproportionately affected by the disease, as they have a greater risk of hospitalization, are more vulnerable to severe infection, and have higher mortality than younger patients. Although effective vaccines have been rapidly developed and administered globally, several clinical trials are ongoing to repurpose existing drugs to combat severe infection. One such drug, rapamycin, is currently under study for this purpose, given its immunosuppressant effects that are mediated by its inhibition of the mechanistic target of rapamycin (mTOR), a master regulator of cell growth. Consistent with this premise, acute rapamycin administration in young healthy humans blocks or attenuates mTOR and its downstream effectors, leading to the inhibition of muscle protein synthesis (MPS). Skeletal muscle mass declines when MPS is chronically lower than muscle protein breakdown. This is consequential for older people who are more susceptible to anabolic resistance (i.e., the blunting of MPS) due to reduced activity, sedentariness, or bed rest such as that associated with COVID-19 hospitalization, and who have also demonstrated a delayed or blunted ability to regain inactivity-induced muscle loss. The lack of studies investigating rapamycin administration on skeletal muscle in older people, and the emergence of effective antiviral medications against severe infection, may indicate the reduced relevance of drug repurposing for present or future pandemics.

Place, publisher, year, edition, pages
American Physiological Society , 2022. Vol. 322, no 6, p. E551-E555
Keywords [en]
aging, anabolic resistance, mTOR, muscle protein synthesis, SARS-CoV-2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:kth:diva-316306DOI: 10.1152/ajpendo.00064.2022ISI: 000833416300004PubMedID: 35521831Scopus ID: 2-s2.0-85131268947OAI: oai:DiVA.org:kth-316306DiVA, id: diva2:1686845
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QC 20220811

Available from: 2022-08-11 Created: 2022-08-11 Last updated: 2022-08-11Bibliographically approved

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