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Br J Clin Pharmacol
. 2021 Feb 20.
doi: 10.1111/bcp.14792. Online ahead of print.
Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action
Lakshmikirupa Sunderesan 1 , Suvendu Giri 2 3 , Himanshi Singh 2 3 , Suvro Chatterjee 2 3
Affiliations
- PMID: 33609410
- DOI: 10.1111/bcp.14792
Abstract
Aim: SARS-coV-2 pandemic continues to cause an unprecedented global destabilization requiring urgent attention towards drug and vaccine development. Thalidomide, a drug with known anti-inflammatory and immunomodulatory effects has been indicated to be effective in treating a SARS-coV-2 pneumonia patient. Here, we study the possible mechanisms through which thalidomide might affect Coronavirus Disease -19 (COVID-19).
Methods: The present study explores the possibility of repurposing thalidomide for the treatment of SARS-coV-2 pneumonia by reanalyzing transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide induced transcriptomic changes in transformed lung and hematopoietic models as procured from databases, and further comparing them with the transcriptome of primary endothelial cells.
Results: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signaling, NOD-like receptor signaling, Toll-like receptor (TLR) signaling, leukocyte differentiation and innate immunity, the processes which are aberrantly regulated in severe COVID-19 patients.
Conclusion: The present study indicates thalidomide analogs as a "better fit" for treating severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the COVID-19.
Keywords: Angiogenesis; COVID-19; Endothelium; Immune Response; Inflammation; Lenalidomide; SARS-coV-2; Thalidomide.