Other substances

Rapamycin

A natural macrocyclic lactone and inhibitor of mammalian Target Of Rapamycin complex 1 (mTORC1).

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Rapamycin is a natural lactone compound that inhibits the mammalian target of rapamycin (mTOR), which is a pleiotropic regulatory kinase. It has (among other) immunosuppressive properties (NCIt). Rapamycin was suggested to inhibit SARS-CoV-2 infection via mTOR inhibition (although by an unknown mechanism) (Mullen et al., 2021).

Rapamycin on DrugBank
Rapamycin on PubChem
Rapamycin on Wikipedia

Synonyms

Sirolimus

Marketed as

RAPAMUNE

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Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2	in silico		in combination with dactinomycin	Mar/16/2020
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Small molecule	in silico	42.78		Apr/30/2020
Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2 Preprint	human renal cortical epithelial cells			Apr/23/2020
Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches Spike protein Small molecule In silico	in silico	3.22	Predicted to inhibit the SARS-CoV-2 spike protein binding to the host's ACE2 receptor.	Sep/24/2020
Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection Protein factor Small molecule Antibody In silico	in silico (machine learning)	13.49	Considered by the authors to be among the most relevant drugs identified in a machine-learning algorithm-based screening of compounds which considers causal protein-protein interactions, known drug targets, and specific signalling circuits in <a href=	Dec/11/2020
SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition Small molecule In vitro	Vero cells; human lung air-liquid interface cultures; SARS-CoV-2 isolate USA-WA1/2020	12.12	Inhibited SARS-CoV-2 replication in Vero cells and human lung air-liquid interface cultures, possibly through mTORC1 inhibition. Rapamycin was the most potent SARS-CoV-2 inhibitor from the mTORC1 inhibitors tested.	Mar/25/2021

AI-suggested references

Link	Publication date
Improved immunogenicity following the third dose of BNT162b2 mRNA vaccine in heart transplant recipients.	Jul/02/2020
Safety of inactivated COVID-19 vaccine in tuberous sclerosis complex patients with epilepsy treated with rapamycin.	May/19/2020
A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19.	Jul/02/2021
COVID-19 and Sirolimus Treatment in a Kidney Transplant Recipient.	Jul/08/2021
Antineoplastic treatment class modulates COVID-19 mRNA-BNT162b2 vaccine immunogenicity in cancer patients: a secondary analysis of the prospective Vax-On study.	Nov/27/2021
PI3K/Akt/mTOR pathway: a potential target for anti-SARS-CoV-2 therapy	Feb/24/2022
Complete recovery from COVID-19 of a kidney-pancreas transplant recipient: potential benefit from everolimus?	Jan/11/2021
Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2.	Oct/26/2020
Structural Analysis of SARS-CoV-2 ORF8 Protein: Pathogenic and Therapeutic Implications	Sep/06/2021
Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site	May/14/2020
Rapamycin: Drug Repurposing in SARS-CoV-2 Infection.	Mar/05/2021
Computational identification of host genomic biomarkers highlighting their functions, pathways and regulators that influence SARS-CoV-2 infections and drug repurposing.	Mar/11/2022
Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling	Jan/10/2022
Azithromycin in viral infections	Sep/23/2020
The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19	Feb/03/2021
Transcriptional landscape of SARS-CoV-2 infection dismantles pathogenic pathways activated by the virus, proposes unique sex-specific differences and predicts tailored therapeutic strategies	Dec/15/2021
mTOR inhibition and p53 activation, microRNAs: The possible therapy against pandemic COVID-19.	Jun/30/2020
Rapamycin as a potential repurpose drug candidate for the treatment of COVID-19	Nov/11/2021
Kinase inhibitors developed for treatment of hematologic malignancies: implications for immune modulation in COVID-19	Oct/02/2021
Pharmacological Modulators of Autophagy as a Potential Strategy for the Treatment of COVID-19.	Apr/15/2021
Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals.	Dec/18/2021
Genomic discovery of an evolutionarily programmed modality for small-molecule targeting of an intractable protein surface	Mar/01/2022
Inhaled biguanides and mTOR inhibition for influenza and coronavirus (Review)	Mar/29/2020
Identification of host transcriptome-guided repurposable drugs for SARS-CoV-1 infections and their validation with SARS-CoV-2 infections by using the integrated bioinformatics approaches	Apr/07/2022
Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model	Feb/16/2021
Tiotropium Is Predicted to Be a Promising Drug for COVID-19 Through Transcriptome-Based Comprehensive Molecular Pathway Analysis	Jul/20/2020
Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials.	May/06/2021
Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights	Dec/11/2020
Immunoregulation with mTOR inhibitors to prevent COVID-19 severity: A novel intervention strategy beyond vaccines and specific antiviral medicines	May/22/2020
Early clinical experience with nirmatrelvir/ritonavir for the treatment of COVID-19 in solid organ transplant recipients	Dec/03/2021
mTOR inhibition: a double-edged sword in patients with COVID-19?	Feb/20/2022
Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis	Jul/12/2021
Computational drug repurposing study of the RNA binding domain of SARS-CoV-2 nucleocapsid protein with antiviral agents	Dec/30/2020
Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses	Sep/22/2021
Repurposing of the approved small molecule drugs in order to inhibit SARS-CoV-2 S protein and human ACE2 interaction through virtual screening approaches	Nov/01/2020

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04948203	Assessing the Efficacy of Sirolimus in Patients With COVID-19 Pneumonia for Prevention of Post-COVID Fibrosis	Recruiting	Phase 2\|Phase 3	Jul/09/2021	Jun/01/2022
Alternative id - IRB21-0400 Interventions - Drug: Sirolimus Study type - Interventional Study results - No Results Available Locations - University of Chicago, Chicago, Illinois, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Prevention Enrollment - 60 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Prevalence of Pulmonary Fibrosis as evidenced by CT scan\|10% Threshold for Pulmonary Fibrosis evidenced by CT scan\|Qualitative Fibrotic markers on chest CT\|Quantitative Fibrosis Score on chest CT\|Duration of Increased Supplemental Oxygen from Baseline\|Pulmonary Function Test impairment
NCT04371640	Sirolimus in COVID-19 Phase 1	Withdrawn	Phase 1	Jul/06/2020	Jul/30/2021
Alternative id - 15680 Interventions - Drug: Sirolimus 1 MG/ML\|Drug: Placebo Study type - Interventional Study results - No Results Available Locations - Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 0 Age - 18 Years to 65 Years (Adult, Older Adult) Outcome measures - Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment\|Change in SARS-CoV-2 viral burden at days 1-6\|Rate of treatment emergent adverse events
NCT04461340	Efficacy and Safety of Sirolimus in COVID-19 Infection	Recruiting	Phase 2	Aug/15/2020	Nov/30/2020
Alternative id - sirolimus in COVID 19 Interventions - Drug: Sirolimus Study type - Interventional Study results - No Results Available Locations - Faculty of Medicine, Alexandria university, Egypt, Alexandria, Egypt Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Single (Participant)\|Primary Purpose: Treatment Enrollment - 40 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Time to clinical recovery\|Viral clearance\|radiological lung extension\|drug adverse events\|28 day mortality\|intensive care unit (ICU) admission rate\|Duration of hospital stay
NCT04482712	Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of ARDS	Withdrawn	Phase 1\|Phase 2	Apr/01/2021	Jan/01/2023
Alternative id - HSC20200489H Interventions - Drug: Rapamycin\|Drug: Placebo Study type - Interventional Study results - No Results Available Locations - University Hospital System, San Antonio, Texas, United States\|Audie L Murphy Memorial Veterans Hospital, San Antonio, Texas, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Double (Participant, Investigator)\|Primary Purpose: Treatment Enrollment - 0 Age - 60 Years and older (Adult, Older Adult) Outcome measures - Survival rate\|Change in Clinical Status assessed by the World Health Organization (WHO) scale\|Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale
NCT04374903	Hydroxychloroquine in Combination With Sirolimus and Dexamethasone for Treating COVID-19 Patients	Not yet recruiting	Not Applicable	Dec/01/2021	Sep/01/2022
Alternative id - 20 KHCC 74 Interventions - Drug: HCQ & AZ vs HCQ+SIR Study type - Interventional Study results - No Results Available Locations - King Hussein Cancer Center, Amman, Jordan Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 58 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Time to Clinical improvement (TTCI)\|Clinical failure defined as death or need for Intubation and mechanical ventilation\|Adverse effects\|QT interval prolongation\|Failure to continue assigned therapy\|Time to viral clearance
NCT04341675	Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia	Recruiting	Phase 2	Apr/24/2020	Sep/01/2020
Alternative id - 2020-0337 Interventions - Drug: Sirolimus\|Drug: Placebo Study type - Interventional Study results - No Results Available Locations - Loyola University Medical Center, Chicago, Illinois, United States\|University of Cincinnati, Cincinnati, Ohio, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 30 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Proportion of patients who are alive and free from advanced respiratory support measures at day 28.\|Proportion of patients who require escalation in care\|Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)\|Proportion of patients surviving to hospital discharge\|Drug safety profile\|Duration of advanced respiratory support\|Duration of hospital stay\|Time from treatment initiation to death\|Time to resolution of fever\|Proportion of patients who require initiation of off-label therapies

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