Title:Screening of Natural Compounds Against SOD1 as a Therapeutic Target
for Amyotrophic Lateral Sclerosis
Volume: 19
Issue: 10
Author(s): Sonu Pahal, Amit Chaudhary and Sangeeta Singh*
Affiliation:
- Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagarj, Uttar Pradesh 211015, India
Keywords:
Virtual Screening, neurodegenerative disease, molecular docking, ADMET, molecular dynamic simulation, amyotrophic lateral sclerosis
Abstract:
Background: Amyotrophic lateral sclerosis (ALS) is an uncommon and progressive neurological
illness that predominantly includes the neurons liable for voluntary muscular activities. Starting from
weakness or stiffness in muscles, this gradually exploits the strength and ability to speak, eat, move, and
even breathe. Its exact mechanism is still not clear, but mutations in the SOD1 gene have been reported to
cause ALS, and some studies also found involvement of SOD1 overexpression in the pathogenesis of
ALS. As of now, there is no remedy available for its cure.
Objective: The objective of this study is to identify the potential inhibitors for wild type 1HL5, l113T
mutant, and A4V mutant of SOD1 (Superoxide Dismutase 1) protein.
Methods: In this study, in silico approaches like virtual screening, molecular docking, pharmacokinetic
parameters study, and molecular dynamics simulation were used to identify the best potential inhibitors
against wild type and mutant SOD1 protein.
Results: On the basis of binding affinity and binding energy, the top three compounds
ZINC000095486263, ZINC000095485989, and ZINC000028462577 were observed as the best compounds.
In the case of 1HL5, ZINC000095486263 had the highest binding affinity with docking score -
10.62 Kcal/mol, 1UXM with ZINC000095485989 had the highest docking score -12.03 Kcal/mol, and
4A7V with ZINC000028462577 was found -11.72 Kcal/mol. Further, Molecular Dynamic Simulations
(MDS) results showed that the ZINC000095486263, ZINC000095485989, and ZINC000095485956
compounds were formed a stable complex with 1HL5, 1UXM, and 4A7V respectively.
Conclusion: After analyzing the results, we hereby conclude that natural compounds such as
ZINC000095486263, ZINC000095485989, and ZINC000095485956 could be used as a potential inhibitor
of 1HL5, 1UXM, and 4A7V respectively for ALS treatment and could be used as a drug. Further, In
vivo/vitro study of these compounds could be a future direction in the field of drug discovery.
