In Silico insight of Cystic Fibrosis and its invitro diagnostic potential using Karakoram clay extracted Silica Nanoparticles

Abstract

Cystic fibrosis is life threatening hereditary disorder in which the chloride channels present in membrane becomes dysfunctional. Cystic fibrosis transmembrane conductance regulator genes produce CFTR protein that is responsible for the transport of chloride and sodium ion across the membranes. CFTR consist of multiple domains i.e., transmembrane domain, nucleotide binding domains and regulatory domain. There are multiple Mutations in CFTR gene lead to the defective ion exchange affecting the multiple organs. The K95Q mutation in the CFTR is a Class IV mutation which is characterized by reduced chloride conduction across the membrane. Three FDA approved drugs Ivacaftor, Tezacaftor and Elexacaftor, that are being used for the treatment of G551D and F508 mutations, are selected as a possible treatment for K95Q mutation. Bioinformatics and computational software were used for the molecular docking, visualization, and analysis of the drug ligands interactions with both wildtype and mutant CFTR with K95Q mutation. Furthermore, silica nanoparticles were extracted from Karakoram clay in order to get some insight into their diagnostic potential. They were characterized through SEM and FTIR. Silica solution was then mixed with NaCl solution to determine the adsorptive properties of SiNPs. The amount of Chloride ions adsorbed was later determined through titration and the results demonstrated that SiNPs have the capacity to adsorb chloride ions to themselves making it possible for them to be used in diagnostic tools for CF and even in drug delivery of the drugs observed in our in silico studies.