Abstract
Emergence of vector borne diseases has continued to take toll on millions of lives since its inception. The use of insecticides began as vector control strategy in the early 1900’s but the menace of insects is still prevalent. Additionally, the inadequate use of organophosphates and carbamates which target acetylcholine esterase (AChE), are known to develop resistance amongst vectors of transmission and are toxic to humans. In this study, extensive computational screening was performed using homology modelling, molecular docking, molecular dynamics (MD) simulation and free energy change calculation, which highlighted curcumin as a lead molecule out of ~ 1700 phytochemicals against Culex pipiens AChE. In vivo larvicidal activity was carried out along with in vivo and in vitro AChE inhibition assay to determine the biochemical efficacy of curcumin. Our study reveals that curcumin induces mortality in Cx. pipiens at an early stage of its life cycle by AChE inhibition. This also underlines the use of curcumin as a coming-age natural product insecticide.
Highlights
Vector borne disease are one of the major health problems in the world, accounting for more than 17% of all infectious diseases (World Health Organisation, 2018)[1]
All these parameters conclusively help to identify curcumin as a lead compound from all the ~ 1700 phytochemicals screened from the IMMPAT database to be the inhibitor of modelled Cx pipiens AChE1 and this was further validated through molecular dynamics (MD) simulations
On affirming by in vitro studies, we performed the in vivo enzyme inhibition assay, where we found that acetylcholine esterase (AChE) inhibition was observed when larvae were incubated for 30 min in solutions of malathion (Fig. 9c) and curcumin (Fig. 9d) in the concentrations ranging from 50 to 250 ppm
Summary
All these parameters conclusively help to identify curcumin as a lead compound from all the ~ 1700 phytochemicals screened from the IMMPAT database to be the inhibitor of modelled Cx pipiens AChE1 and this was further validated through MD simulations. The large presence of tails of N and C terminals showcase higher fluctuations in the corresponding peaks while secondary structure elements like α helices and β strands are usually more rigid and show less fluctuation In this case, the docked complexes of modelled AChE1-ACh (Fig. 5b), modelled AChE1-malathion (Fig. 5d), and modelled AChE1-curcumin (Fig. 5f) depict protein interaction with the ligands and trends of RMSF correspond for ACh and malathion while for curcumin the value suggests better stability. From the entire study it can be well deduced that, curcumin exhibit larvicidal activity and can inhibit Cx. pipiens larval AChE in the competitive manner which ultimate serves as its mode of action for larvicidal activity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
