Title:In silico Insights on IL-6: A Potential Target for Multicentric Castleman Disease
VOLUME: 16 ISSUE: 5
Author(s):Abhishek Aher, Trishang Udhwani, Ravina Khandelwal, Akanksha Limaye, Tajamul Hussain, Anuraj Nayarisseri* and Sanjeev Kumar Singh*
Affiliation:In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, Center of Excellence in Biotechnology Research, College of Science, King Saud University, Riyadh, In Silico Research Laboratory, Eminent Biosciences, Mahalakshmi Nagar, Indore – 452010, Madhya Pradesh, Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi-630 003, Tamil Nadu
Keywords:IL-6 Inhibitors, multicentric castleman disease, virtual screening, molecular docking, ADMET, toxicity study.
Abstract:
Background: Multicentric Castleman Disease (MCD) is a confrontational lymphoproliferative
disorder described by symptoms such as lymph node proliferation, unwarranted secretion of
inflammatory cytokines, hyperactive immune system, and in severe cases, multiple organ dysfunction.
Interleukin-6 (IL-6) is a pleiotropic cytokine which is involved in a large range of physiological
processes in our body such as pro-inflammation, anti-inflammation, differentiation of T-cells
and is reported to be a key pathological factor in MCD. In the case of MCD, it was observed that
IL-6 is overproduced from T-cells and macrophages which disturb Hepcidin, a vital regulator of
iron trafficking in macrophage. The present study endeavour to expound the inhibitor which binds
to IL-6 protein receptor with high affinity.
Methods: MolegroVirtual Docker software was employed to find the best-established drug from
the list of selected inhibitors of IL-6. This compound was subjected to virtual screening against
PubChem database to get inhibitors with a very similar structure. These inhibitors were docked to
obtain a compound binding with high affinity to the target protein. The established compound and
the virtual screened compound were subjected to relative analysis of interactivity energy variables
and ADMET profile studies.
Results: Among all the selected inhibitors, the virtual screened compound PubChem CID:
101119084 is seen to possess the highest affinity with the target protein. Comparative studies and
ADMET analysis further implicate this compound as a better inhibitor of the IL-6 protein.
Conclusion: Hence, this compound recognized in the study possesses high potential as an IL-6 inhibitor
which might assist in the treatment of Multicentric Castleman Disease and should be examined
for its efficiency by in vivo studies.
