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Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action
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  • Lakshmikirupa Sundaresan,
  • Suvendu Giri,
  • Himanshi Singh,
  • Suvro Chatterjee
Lakshmikirupa Sundaresan
Hospital for Sick Children

Corresponding Author:[email protected]

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Suvendu Giri
AU-KBC Research Centre
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Himanshi Singh
AU-KBC Research Centre
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Suvro Chatterjee
AU-KBC Research Centre
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Abstract

Background and Purpose: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization. There is an urgent need to develop vaccines or identify molecules to treat severe cases and repurposing of drugs is the best approach at this hour. Thalidomide, despite having an infamous history has been successfully repurposed and tested for various disease conditions including inflammatory diseases and tumor. Few reports emphasize the use of thalidomide with a SARS-coV-2 pneumonia patient being successfully treated with thalidomide. Experimental Approach: A meta-analysis comparing the transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide-induced transcriptomic changes in transformed lung, endothelial and hematopoietic models was performed. Key Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, TLR signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients. In addition, we show the similarities between the expression profiles of SARS-coV-2 infected lung and systemic lupus erythematous. Conclusion and Implications: The present study recommends thalidomide analogs as a “better fit” to treat severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the Coronavirus disease-2019 (COVID-19).
16 Jun 2020Submitted to British Journal of Clinical Pharmacology
16 Jun 2020Submission Checks Completed
16 Jun 2020Assigned to Editor
29 Jun 2020Reviewer(s) Assigned
19 Sep 2020Review(s) Completed, Editorial Evaluation Pending
21 Sep 2020Editorial Decision: Revise Major
30 Nov 20201st Revision Received
01 Dec 2020Submission Checks Completed
01 Dec 2020Assigned to Editor
01 Dec 2020Review(s) Completed, Editorial Evaluation Pending
20 Jan 2021Reviewer(s) Assigned
25 Jan 2021Editorial Decision: Revise Minor
27 Jan 20212nd Revision Received
28 Jan 2021Submission Checks Completed
28 Jan 2021Assigned to Editor
28 Jan 2021Review(s) Completed, Editorial Evaluation Pending
08 Feb 2021Editorial Decision: Accept
20 Feb 2021Published in British Journal of Clinical Pharmacology. 10.1111/bcp.14792