Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19.

Article Details

Citation

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
DrugTargetKindOrganismPharmacological ActionActions
AcalabrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details
DasatinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
EvobrutinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
FostamatinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
IbrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details
Inositol 1,3,4,5-TetrakisphosphateTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
SpebrutinibTyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
XL418Tyrosine-protein kinase BTKProteinHumans
Unknown
Inhibitor
Details
ZanubrutinibTyrosine-protein kinase BTKProteinHumans
Yes
Inhibitor
Details