In silico analysis and molecular docking studies of natural compounds of Withania somnifera against bovine NLRP9

Aarif Ali; Gh Jeelani Mir; Aadil Ayaz; Illiyas Maqbool; Sheikh Bilal Ahmad; Saima Mushtaq; Altaf Khan; Tahir Maqbool Mir; Muneeb U Rehman

doi:10.1007/s00894-023-05570-z

In silico analysis and molecular docking studies of natural compounds of Withania somnifera against bovine NLRP9

J Mol Model. 2023 May 8;29(6):171. doi: 10.1007/s00894-023-05570-z.

Authors

Aarif Ali¹, Gh Jeelani Mir¹, Aadil Ayaz², Illiyas Maqbool³, Sheikh Bilal Ahmad⁴, Saima Mushtaq⁵, Altaf Khan⁶, Tahir Maqbool Mir⁷, Muneeb U Rehman⁸

Affiliations

¹ Department of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Hazratbal, Srinagar, 190006, J&K, India.
² Department of Microbiology, SKIMS Medical College Bemina, Srinagar, 190018, J&K, India.
³ Department of Microbiology, Government Medical College, Baramulla, 193101, J&K, India.
⁴ Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Kashmir (SKUAST-K), Shuhama, Srinagar, 190006, J&K, India.
⁵ Veterinary Microbiology Department, Indian Veterinary Research Institute (IVRI), Bareilly, Uttar Pradesh, 243122, India.
⁶ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
⁷ National Centre for Natural Products Research, University of Mississippi, Oxford, MS, 38677, USA.
⁸ Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. muneebjh@gmail.com.

Abstract

Context: NLRP9 is a member of nucleotide-binding domain leucine-rich repeat-containing receptors and is found to be associated with many inflammatory diseases. In the current scenario, the identification of promising anti-inflammatory compounds from natural sources by repurposing approach is still relevant for the early prevention and effective management of the disease.

Methods: In the present study, we docked bioactives of Ashwagandha (Withanoside IV, Withanoside V, Withanolide A, Withanolide B, and Sitoindoside IX) and two control drugs against bovine NLRP9 protein. ADME/T analysis was used to determine the physiochemical properties of compounds and standard drugs. Molecular modeling was used to evaluate the correctness and quality of protein structures. In silico docking analysis revealed Withanolide B had the highest binding affinity score of -10.5 kcal/mol, whereas, among control drugs, doxycycline hydrochloride was most effective (-10.3 kcal/mol). The results of this study revealed that bioactives of Withania somnifera could be promising inhibitors against bovine NLRP9. In the present study, molecular simulation was used to measure protein conformational changes over time. The Rg value was found to be 34.77A°. RMSD and B-factor were also estimated to provide insights into the flexibility and mobile regions of protein structure. A functional protein network interaction was constructed from information collected from non-curative sources as protein-protein interactions (PPI) that play an important role in determining the function of the target protein and the ability of the drug molecule. Thus, in the present situation, it is important to identify bioactives with the potential to combat inflammatory diseases and provide strength and immunity to the host. However, there is still a need to study in vitro and in vivo to further support these findings.

Keywords: ADMET; Docking; Electrostatic; In silico; NLRP9; STRING; Simulation; Withania somnifera.

MeSH terms

Animals
Cattle
Computer Simulation
Molecular Docking Simulation
Withania* / chemistry
Withania* / metabolism