Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19.
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Kaliamurthi S, Selvaraj G, Selvaraj C, Singh SK, Wei DQ, Peslherbe GH
Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19.
Int J Mol Sci. 2021 Jun 30;22(13). pii: ijms22137071. doi: 10.3390/ijms22137071.
- PubMed ID
- 34209188 [ View in PubMed]
- Abstract
Coronavirus disease (COVID)-19 is the leading global health threat to date caused by a severe acute respiratory syndrome coronavirus (SARS-CoV-2). Recent clinical trials reported that the use of Bruton's tyrosine kinase (BTK) inhibitors to treat COVID-19 patients could reduce dyspnea and hypoxia, thromboinflammation, hypercoagulability and improve oxygenation. However, the mechanism of action remains unclear. Thus, this study employs structure-based virtual screening (SBVS) to repurpose BTK inhibitors acalabrutinib, dasatinib, evobrutinib, fostamatinib, ibrutinib, inositol 1,3,4,5-tetrakisphosphate, spebrutinib, XL418 and zanubrutinib against SARS-CoV-2. Molecular docking is conducted with BTK inhibitors against structural and nonstructural proteins of SARS-CoV-2 and host targets (ACE2, TMPRSS2 and BTK). Molecular mechanics-generalized Born surface area (MM/GBSA) calculations and molecular dynamics (MD) simulations are then carried out on the selected complexes with high binding energy. Ibrutinib and zanubrutinib are found to be the most potent of the drugs screened based on the results of computational studies. Results further show that ibrutinib and zanubrutinib could exploit different mechanisms at the viral entry and replication stage and could be repurposed as potential inhibitors of SARS-CoV-2 pathogenesis.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Acalabrutinib Tyrosine-protein kinase BTK Protein Humans YesInhibitorDetails Dasatinib Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails Evobrutinib Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails Fostamatinib Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails Ibrutinib Tyrosine-protein kinase BTK Protein Humans YesInhibitorDetails Inositol 1,3,4,5-Tetrakisphosphate Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails Spebrutinib Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails XL418 Tyrosine-protein kinase BTK Protein Humans UnknownInhibitorDetails Zanubrutinib Tyrosine-protein kinase BTK Protein Humans YesInhibitorDetails