4.4 Review

Can We Use mTOR Inhibitors for COVID-19 Therapy?

Journal

COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
Volume 25, Issue 11, Pages 1805-1808

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1386207325666211130140923

Keywords

mTOR inhibitors; COVID-19; SARS-CoV-2; sirolimus; everolimus; temsirolimus; rapamycin

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Infection by SARS-CoV-2 leads to acute inflammation, and mTOR protein can be modulated to alleviate this inflammation. The mTOR protein has critical roles in protein synthesis, cell proliferation, and immune suppression, making mTOR inhibitors promising in the treatment of viral infections.
Infection by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes acute inflammation due to extensive replication of the virus in the epithelial cells of the upper and lower respiratory system. The mammalian target of rapamycin (mTOR) is a l signalling protein with critical functions in cell growth, metabolism, and proliferation. It is known for its regulatory functions in protein synthesis and angiogenesis cascades. The structure of mTOR consists of two distinct complexes (mTORC1 and mTORC2) with diverse functions at different levels of the signalling pathway. By activating mRNA translation, the mTORC1 plays a key role in regulating protein synthesis and cellular growth. On the other hand, the functions of mTORC2 are mainly associated with cell proliferation and survival. By using an appropriate inhibitor at the right time, mTOR modulation could provide immunosuppressive opportunities as antirejection regimens in organ transplantation as well as in the treatment of autoimmune diseases and solid tumours. The mTOR also has an important role in the inflammatory process. Inhibitors of mTOR might indeed be promising agents in the treatment of viral infections. They have further been successfully used in patients with severe influenza A/H1N1 pneumonia and acute respiratory failure. The officially accepted mTOR inhibitors that have undergone clinical testing are sirolimus, everolimus, temsirolimus, and tacrolimus. Thus, further studies on mTOR inhibitors for SARS-CoV-2 infection or COVID-19 therapy are well merited.

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