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Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19
Amjad Husain1, Siddappa N Byrareddy2
1Centre for Science and Society, Indian Institute of Science Education and Research (IISER), Bhopal, MP, India; Innovation and Incubation Centre for Entrepreneurship, Indian Institute of Science Education and Research (IISER), Bhopal, MP, India.
Abstract:
The novel human coronavirus-2 (HCoV-2), called SARS-CoV-2, is the causative agent of Coronavirus Induced Disease (COVID-19) and has spread causing a global pandemic. Currently, there is no vaccine to prevent infection nor any approved drug for the treatment. The development of a new drug is time-consuming and cannot be relied on as a solution in combatting the immediate global challenge. In such a situation, the drug repurposing becomes an attractive solution to identify the potential of COVID-19 treatment by existing drugs, which are approved for other indications. Here, we review the potential use of rapamycin, an mTOR (Mammalian Target of Rapamycin) inhibitor that can be repurposed at low dosages for the treatment of COVID-19. Rapamycin inhibits protein synthesis, delays aging, reduces obesity in animal models, and inhibits activities or expression of pro-inflammatory cytokines such as IL-2, IL-6 and, IL-10. Overall, the use of rapamycin can help to control viral particle synthesis, cytokine storms and contributes to fight the disease by its anti-aging and anti-obesity effects. Since, rapamycin targets the host factors and not viral machinery, it represents a potent candidate for the treatment of COVID-19 than antiviral drugs as its efficacy is less likely to be dampened with high mutation rate of viral RNA. Additionally, the inhibitory effect of rapamycin on cell proliferation may aid in reducing viral replication. Therefore, by drug repurposing, low dosages of rapamycin can be tested for the potential treatment of COVID-19/SARS-CoV-2 infection.
Insights
Drug repurposing offers a potential COVID-19 treatment using rapamycin, an mTOR inhibitor. This drug may control viral load and cytokine storms, offering a promising therapeutic avenue for SARS-CoV-2 infection.
Area of Science:
- Virology
- Pharmacology
- Immunology
Background:
- SARS-CoV-2 causes COVID-19, a global pandemic with no current vaccines or approved treatments.
- Developing new drugs is time-consuming, necessitating alternative strategies like drug repurposing.
Purpose of the Study:
- To review the potential of rapamycin, an mTOR inhibitor, as a repurposed drug for COVID-19 treatment.
- To explore rapamycin's mechanisms of action against SARS-CoV-2 and its host factors.
Main Methods:
- Literature review of rapamycin's known effects on protein synthesis, aging, obesity, and inflammation.
- Analysis of rapamycin's potential to target host factors relevant to SARS-CoV-2 replication and pathogenesis.
Main Results:
- Rapamycin inhibits protein synthesis, reduces pro-inflammatory cytokines (IL-2, IL-6, IL-10), and possesses anti-aging and anti-obesity effects.
- As a host-directed therapy, rapamycin's efficacy is less susceptible to viral mutations compared to direct antivirals.
- Inhibition of cell proliferation by rapamycin may reduce viral replication.
Conclusions:
- Low-dose rapamycin is a potential candidate for repurposed COVID-19 treatment.
- Rapamycin may combat viral load, cytokine storms, and disease progression through its multifaceted actions.
- Further clinical testing of rapamycin for COVID-19 is warranted.

