Denovo Designing, Virtual Screening and Lead Optimization of Potential Drug Candidate for Herpes Disease
Monica Sharma, Puneet Rawat, Ankita Mehta · Journal of Microbial & Biochemical Technology · 2015
After exhaustive literature survey and database searching, no ligand was found that bind to this target, so automated de-novo drug design strategy was adopted to get a hit molecule.eLEA3D program was used for denovo generation of ligand, which create new molecules by using a library of molecular fragments and by determining best combinations of molecular fragments that fit user-defined physicochemical properties AbstractHerpes simplex virus (HSV1, HSV 2) is a neurotropic and neuroinvasive virus which becomes latent and causes a lifelong infection.HSV-1 and 2 produce infected cell protein (ICP)-47 against MHC class I antigen presentation pathway by inhibiting the transporter associated with antigen processing (TAP).ICP 47 is also responsible for evasive nature of HSV in human immune system.Currently available antiviral drugs and vaccines only slowdowns the infection but it does not cure the infection.In present study, we have in silico designed a potential drug candidate against HSV ICP-47 target through de-novo pathway using eLEA3D.The derived ligand docked with the natural viral receptor ICP-47 showed the binding affinity of -4.07, but it was found toxic in FAF DRUG online ADMET tool, due to presence of high risk imine group.Further manual optimization led to generation of many bioisosteres and final lead structure showed no toxicity and a high binding affinity of -7.53.Our designed lead can act as a potential therapeutic compound against HSV.