Sirolimus to treat SARS-CoV-2 infection: an old drug for a new disease

Romanelli, Antonio; Mascolo, Silvia

doi:10.34172/jrcm.2020.044

Cited by 7 publications

(6 citation statements)

References 6 publications

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“…We also obtained selective immunosuppressants such as: baricitinib, sirolimus, tofacitinib and a calcineurin inhibitor, voclosporin. Sirolimus, a drug used to prevent organ rejection in renal transplants and suggested for COVID-19 also in [ 25 ], was identified in both network analyses, due to its inhibitory effect on MTOR, whereas baricitinib and tofacitinib were identified only in the MOI 0.01 network analysis, due to their inhibitory action on JAK2. Both are used in rheumatoid arthritis, and baricitinib has Food and Drug Administration (FDA) approval for use in COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Network analytics for drug repurposing in COVID-19

Popescu

Martin

et al. 2021

Briefings in Bioinformatics

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To better understand the potential of drug repurposing in COVID-19, we analyzed control strategies over essential host factors for SARS-CoV-2 infection. We constructed comprehensive directed protein–protein interaction (PPI) networks integrating the top-ranked host factors, the drug target proteins and directed PPI data. We analyzed the networks to identify drug targets and combinations thereof that offer efficient control over the host factors. We validated our findings against clinical studies data and bioinformatics studies. Our method offers a new insight into the molecular details of the disease and into potentially new therapy targets for it. Our approach for drug repurposing is significant beyond COVID-19 and may be applied also to other diseases.

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Section: Resultsmentioning

confidence: 99%

Network analytics for drug repurposing in COVID-19

Popescu

Martin

et al. 2021

Briefings in Bioinformatics

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“…The 18-kDa cytoplasmic protein procyclin A is an important cellular biomolecule required for RNA virus replication, and recent studies have shown that non-immunosuppressive analogs, such as alisporivir, inhibit the activity of procyclins (Almasi and Mohammadipanah, 2020 ). Saracatinib, sirolimus, and suramin have also been indicated as therapeutic agents for COVID-19 in recent studies (Romanelli and Mascolo, 2020 ; Salgado-Benvindo et al, 2020 ; Tatar et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

WLLP: A weighted reconstruction-based linear label propagation algorithm for predicting potential therapeutic agents for COVID-19

Chen

Lin²,

Xu³

et al. 2022

Front. Microbiol.

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The global coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV) has led to a huge health and economic crises. However, the research required to develop new drugs and vaccines is very expensive in terms of labor, money, and time. Owing to recent advances in data science, drug-repositioning technologies have become one of the most promising strategies available for developing effective treatment options. Using the previously reported human drug virus database (HDVD), we proposed a model to predict possible drug regimens based on a weighted reconstruction-based linear label propagation algorithm (WLLP). For the drug–virus association matrix, we used the weighted K-nearest known neighbors method for preprocessing and label propagation of the network based on the linear neighborhood similarity of drugs and viruses to obtain the final prediction results. In the framework of 10 times 10-fold cross-validated area under the receiver operating characteristic (ROC) curve (AUC), WLLP exhibited excellent performance with an AUC of 0.8828 ± 0.0037 and an area under the precision-recall curve of 0.5277 ± 0.0053, outperforming the other four models used for comparison. We also predicted effective drug regimens against SARS-CoV-2, and this case study showed that WLLP can be used to suggest potential drugs for the treatment of COVID-19.

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“…Inhibition of mTOR suppresses the cytokine storm, which maybe the cause of hyperinflammatory phase of COVID-19 [133,151]. Inhibition of PI3K/AKT pathway by blocking mTOR has been claimed to be beneficial in SARS-CoV-2 infection [130,152]. Sirolimus also known as rapamycin, an mTOR inhibitor used as an immunosuppressant against transplant rejection, was found to be advantageous in MERS-CoV.…”

Section: Targeting Pi3k/akt In Sars-cov-2: Mechanismsmentioning

confidence: 99%

“…Terrazzano and coworkers claimed everolimus, a rapamycin derivate, to be a potential antiviral agent against SARS-CoV-2 by blocking mTOR in PI3K/AKT pathway. Everolimus may decrease SARS-CoV-2 replication as it does in some other viral infections [152]. Azithromycin, a macrolide antibiotic has been used for its anti-inflammatory and immunomodulatory effects in some respiratory diseases.…”

Section: Targeting Pi3k/akt In Sars-cov-2: Mechanismsmentioning

confidence: 99%

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19

Aleebrahim-Dehkordi

Koochaki

Samami

et al. 2022

Cell Physiol Biochem

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Natural resources have long played a prominent part in conventional treatments as a parental source due to their multifaceted functions and lesser side effects. The diversity of marine products is a significant source of possible bioactive chemical compounds with a wide range of potential medicinal applications. Marine organisms produce natural compounds and new drugs with unique properties are produced from these compounds. A lot of bioactive compounds with medicinal properties are extracted from marine invertebrates, including Peptides, Alkaloids, Terpenoids, Steroids. Thus, it can be concluded that marine ecosystems are endowed with natural resources that have a wide range of medicinal properties, and it is important to examine the therapeutic and pharmacological capabilities of these molecules. So, finding particular inhibitors of the COVID-19 in natural compounds will be extremely important. Natural ingredients, in this light, could be a valuable resource in the progression of COVID-19 therapeutic options. Controlling the immunological response in COVID-19 patients may be possible by addressing the PI3K/Akt pathway and regulating T cell responses. T cell effector activity can be improved by preventing anti-viral exhaustion by suppressing PI3K and Akt during the early anti-viral response. The diversity of marine life is a significant supply of potentially bioactive chemical compounds with a broad range of medicinal uses. In this study, some biologically active compounds from marine organisms capable of inhibiting PI3K/AKT and the possible therapeutic targets from these compounds in viral infection COVID-19 have been addressed.

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Sirolimus to treat SARS-CoV-2 infection: an old drug for a new disease

Cited by 7 publications

References 6 publications

Network analytics for drug repurposing in COVID-19

Network analytics for drug repurposing in COVID-19

WLLP: A weighted reconstruction-based linear label propagation algorithm for predicting potential therapeutic agents for COVID-19

Possible Therapeutic Targets from Derivatives of Natural Marine Products Based on PI3K/AKT Dependent Inhibitors in Viral Infection COVID-19

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