Novel immunological aspects of sirolimus as a new targetedtherapy for COVID-۱۹

Background and Aim : COVID-۱۹ involves a severe inflammatory response from neutrophils,lymphocytes, macrophages, and immune system inductors and also increases inflammatorycytokines, which are a cause of death in patients. Accordingly, mTOR plays a key role in theinherent immune system and increases inflammatory cytokines. Therefore, the inflammatorycytokine production through NF-κB activity and release of IL-۱۰ by activated signal transducerand activator of transcription ۳ (STAT۳) in human monocytes is inhibited via mTOR inhibition.Sirolimus (Rapamycin) is a macrolide molecule produced by Streptomyces Hygoscopius, whichweakens the immune system and paradoxically strengthens T cell activity during pathogeninvasions. Sirolimus is also known to have antibiotic, antitumor, and antifungal effects.Methods : A literature search was conducted using scientific databases such as Web of Science,Medline (PubMed), Scopus, Google Scholar, and Embase. The most relevant articles regardingthe potential effects of sirolimus against COVID-۱۹ were gathered.Results : Another mechanism that places sirolimus as an ideal candidate for COVID-۱۹ treatmentis its inhibitory effect on the mTORC۱ receptor. According to reports, viral protein expression andvirion release have been effectively blocked by sirolimus which is an inhibitor of the mammaliantarget of rapamycin (mTOR). mTOR is a protected Serine/threonine-specific protein kinase thatregulates cell growth and cell cycle progression through Phosphatidyl ۳-kinase (PI۳K) and kinase-B protein. Research on old-aged individuals also showed that the inhibition of mTOR via sirolimusenhanced the individuals’ immune systems.Conclusion : Since COVID-۱۹ engages the human immune system and given the expressedmechanisms, sirolimus can be used as an effective drug in the COVID-۱۹ treatment protocol.Currently, several clinical trials are in the process of evaluating the therapeutic effect of sirolimusin the treatment of COVID-۱۹. However, large-scale clinical trials should confirm routineadministration of sirolimus as a component of a standard treatment protocol for COVID-۱۹.

کلیدواژه ها:

Coronavirus ، COVID-۱۹ ، SARS-CoV-۲ ، Sirolimus ، Rapamycin ، mTOR