Title:Computer-aided Drug Designing for the Identification of High-Affinity Small Molecule Targeting CD20 for the Clinical Treatment of Chronic Lymphocytic Leukemia (CLL)
Volume: 18
Issue: 29
Author(s): Kritika Sinha, Manisha Majhi, Garima Thakur, Khushboo Patidar, Jajoriya Sweta, Tajamul Hussain, Anuraj Nayarisseri*Sanjeev Kumar Singh*
Affiliation:
- In silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh,India
- Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh,Saudi Arabia
Keywords:
Chronic Lymphocytic Leukemia, CD20, Molecular modelling, MODELLER, Molecular Docking, Virtual Screening,
BOILED-Egg plot.
Abstract: Background: Chronic lymphocytic leukemia (CLL) is a B-lineage lymphoid malignancy of
self-reactive cells that are focused to produce polyreactive natural autoantibodies. Its surface protein
marker CD20 plays an important role in the humoral immune response targeting which has emerged as
an attractive therapeutic option for the treatment of CLL. The present study explains the interaction of
the CD20 with its established inhibitors and to discover the compound having high binding affinity
against the target protein receptor. Technically, during the development of new compound through
docking studies, best drug among all pre-exist drugs got filtered, hence in reference to docked best drug
study moved ahead.
Methods: The 3D structure of CD20 was built using homology base fold recognition method using
Smith waterman’s Local alignment and standalone Delta Blast algorithms. 23 established inhibitors
towards CD20 were selected in this present investigation. Among these inhibitors, etoposide (RMSD
value -96.6481) showed high binding capacity with the receptor CD20 which was further subjected to
virtual screening. The said screening presented 380 possible drugs having structural similarity to
etoposide.
Results: The docking studies of the screened drugs separated the compound having PubChem CID:
11753896 (RMSD value -98.5416). Toxicity and interaction profile validated this compound for having
a better affinity with the target protein. Conclusively, this research study says that according to ADMET
profile and BOILED-Egg plot, the compound (PubChem CID: 11753896) obtained from Virtual
Screen could be the best drug in future during the prevention of Chronic Lymphocytic Leukemia.
Conclusion: The compound identified in the present investigation can be subjected further for in vitro
and in vivo studies for ADMET properties and it could optimize a good profile in the field of pharmacy
and bioavailable for suppressing cancer. The pharmacophore study revealed that the drug
CID11753896 is a non-inhibitor of CYP450 microsomal enzymes and was found to be non-toxic, similar
to the established compound CID36462. It has a lower LD50 value of 2.5423mol/kg as compared to
the established compound whose LD50 value is 2.9588mol/kg. Also, the compound was found to be
non-carcinogenic.
