Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

Abstract

Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world’s acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation.

PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy

“…Rapamycin: a proper mTORC1 inhibitor mTOR interacts with several proteins, which later form two complexes: mTORC1 (sensitive to rapamycin) and mTORC2 (non-sensitive to rapamycin) [7]. Various mTOR pathway inhibitors (such as rapamycin) have been presented up until now [8]. AMPK is considered a significant regulator of mTORC1.…”

“…mTOR (also known as the mechanistic target of rapamycin) is a serine-threonine protein kinase involved in various biological processes, including metabolism pathways, protein synthesis, cell proliferation, autophagy, and cell growth [7]. Since mTOR is involved in initiating the inflammatory response, the inhibitory compounds of this pathway (such as rapamycin) can reduce the severity of the disease [8].…”

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…PRAS40 blocks binding of p70 ribosomal S6 kinase (p70S6K) and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) to Raptor that can affect mTORC1 activity [165,166]. Rapamycin mTORC1 [24] as well inhibits activation of mTORC1 [162,[167][168][169][170]. mTORC2 has some different components when compared to mTORC1 [171].…”

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

“…mTORC1 activity is controlled through a number of pathways that includes PRAS40 by blocking the association of p70 ribosomal S6 kinase (p70S6K) and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) with Raptor [167,168]. Rapamycin is an agent that can inhibit mTOR activity [164,[169][170][171][172]. Rapamycin blocks the activity of mTORC1 through its association with immunophilin FK-506-binding protein 12 (FKBP12) that attaches to the FKBP12 -rapamycin-binding domain (FRB) at the carboxy (C) -terminal of mTOR to impede the FRB domain of mTORC1 [4].…”