PMID- 35521831
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20221207
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 322
IP  - 6
DP  - 2022 Jun 1
TI  - Challenges of rapamycin repurposing as a potential therapeutic candidate for 
      COVID-19: implications for skeletal muscle metabolic health in older persons.
PG  - E551-E555
LID - 10.1152/ajpendo.00064.2022 [doi]
AB  - 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.
FAU - Lees, Matthew J
AU  - Lees MJ
AUID- ORCID: 0000-0003-1422-0154
AD  - Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Hodson, Nathan
AU  - Hodson N
AUID- ORCID: 0000-0003-1330-4030
AD  - Department of Sport and Exercise Sciences, Musculoskeletal Science and Sports 
      Medicine Research Centre, Manchester Metropolitan University, Manchester, United 
      Kingdom.
FAU - Tinline-Goodfellow, Cassidy T
AU  - Tinline-Goodfellow CT
AUID- ORCID: 0000-0002-9367-1852
AD  - Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Fung, Hugo J W
AU  - Fung HJW
AUID- ORCID: 0000-0001-7833-7672
AD  - Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, 
      University of Toronto, Toronto, Ontario, Canada.
FAU - Elia, Antonis
AU  - Elia A
AUID- ORCID: 0000-0002-5991-0733
AD  - Division of Environmental Physiology, School of Chemistry, Bioengineering and 
      Health, KTH Royal Institute of Technology, Stockholm, Sweden.
FAU - Moore, Daniel R
AU  - Moore DR
AUID- ORCID: 0000-0001-5865-4398
AD  - Department of Exercise Sciences, Faculty of Kinesiology and Physical Education, 
      University of Toronto, Toronto, Ontario, Canada.
LA  - eng
PT  - Editorial
PT  - Research Support, Non-U.S. Gov't
DEP - 20220506
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Muscle Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Drug Repositioning
MH  - Humans
MH  - Muscle Proteins
MH  - Muscle, Skeletal
MH  - SARS-CoV-2
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases
MH  - *COVID-19 Drug Treatment
PMC - PMC9169843
OTO - NOTNLM
OT  - SARS-CoV-2
OT  - aging
OT  - anabolic resistance
OT  - mTOR
OT  - muscle protein synthesis
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2022/05/07 06:00
MHDA- 2022/06/07 06:00
PMCR- 2022/05/06
CRDT- 2022/05/06 07:22
PHST- 2022/05/07 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2022/05/06 07:22 [entrez]
PHST- 2022/05/06 00:00 [pmc-release]
AID - E-00064-2022 [pii]
AID - 10.1152/ajpendo.00064.2022 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2022 Jun 1;322(6):E551-E555. doi: 
      10.1152/ajpendo.00064.2022. Epub 2022 May 6.