Repurposing Thalidomide, its Analogue and Apremilast for Possible Antiviral in Situation of Severe COVID Cytokine Syndrome

Abstract

BACKGROUND: COVID-19, caused by SARS-corona virus-2, is a global wide expanded public health risk at a bizarre level. In this current situation, COVID-19 became a serious emerging pandemic. Choosing drug reusing is a crucial step in identifying the new uses of old established drugs. To achieve a significant and healthy way of treatment in COVID patients within a short duration, drug repurposing is a novel method. OBJECTIVE: The present study concentrated on the molecular docking of thalidomide and its analogues and Apremilast against Coronavirus infectious symptoms, evaluated on virus proteins (Spike Protein, 3cl Protease, Nucleocapsids). METHODS: The present study explores the possibility of repurposing thalidomide for the treatment of SARS-COV-2 infection by assessing and confirming with docking affinity scores of thalidomide & its analogues and Apremilast, with spike protein, 3cl protease, and nucleocapsids. RESULTS: From the study results, thalidomide, pomalidomide, lenalidomide, and Apremilast exhibited better binding affinity to N Protein (4KXJ), Protease (4WY3) and Spike Protein (5WRG). In comparison of targets, N Protein - 4KXJ is the best for the four ligands. It is finalized that all four ligands (Thalidomide - -8.6, Pomalidomide - -8.8, Lenalidomide,and - -8.2,and Apremilast - -8.1) have good docking scores with the target N Protein. CONCLUSION: The present study shows confirmation that thalidomide and its analogues and apremilast as a better fit for treating high risk patients of COVID -19 viral infection which are supposed to promote beneficial effects for both respiratory illnesses like COVID-19 symptoms as well as improve the pathological state of condition.

The role of cell death in SARS-CoV-2 infection

“… 152 , 160 Besides, phase-III clinical studies on the PDE4 selective-inhibitors ensifentrine and apremilast on treating COVID-19 are underway (NCT04590586, NCT02735707). 161 …”

“… 149 Apremilast PDE4 NETosis A PDE4 selective inhibitor. 161 DNase-I NETs NETosis Dissolves thrombogenic NETs. 162 Dipyridamole PDE NETosis A PDE inhibitor.…”

“…152,160 Besides, phase-III clinical studies on the PDE4 selective-inhibitors ensifentrine and apremilast on treating COVID-19 are underway (NCT04590586, NCT02735707). 161 NETs degradation and elimination is also the appropriate pathway for investigation, thus reducing the NETs burden. As enzymes that degrade DNA, deoxyribonucleases (DNases) play critical roles in degrading NETs products.…”

The Latest Ideas of Medical and Biological Developments and Improvement of Psychological Sciences by Scientists

“…• Cancer therapy: For instance, tamoxifen, originally developed as a selective estrogen receptor modulator (SERM) for breast cancer, has also been repurposed for reducing the risk of breast cancer in high-risk individuals [244]. Additionally, drugs such as thalidomide and lenalidomide, initially developed for other indications, have been successfully repurposed for the treatment of multiple myeloma [245]. Imatinib, initially approved for the treatment of chronic myeloid leukemia (CML), has shown efficacy in other cancers as well.…”