title: Virtual screening of phytochemicals to novel targets in Haemophilus ducreyi towards the treatment of Chancroid.
abstract: Conventionally, drugs are discovered by testing chemically synthesized compounds against a battery of in vivo biological screens. Information technology and Omic science enabled us for high throughput screening of compound libraries against biological targets and hits are then tested for efficacy in cells or animals. Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin. So, there is a requirement to develop an efficient drug to combat Chancroid that can also diminish HIV infection. In-silico screening of potential inhibitors against the target may facilitate in detection of the novel lead compounds for developing an effective chemo preventive strategy against Haemophilus ducreyi. The present study has investigated the effects of approximately 1100 natural compounds that inhibit three vital enzymes viz. Phosphoenolpyruvate phosphotransferase, Acetyl-coenzyme A carboxylase and Fructose 1, 6-bisphosphatase of Haemophilus ducreyi in reference to a commercial drug Rifabutin. Results reveal that the lead compound uses less energy to bind to target. The lead compound parillin has also been predicted as less immunogenic in comparison to Rifabutin. Further, better molecular dynamics, pharmacokinetics, pharmacodynamics and ADME-T properties establish it as an efficient chancroid preventer.
authors.affiliation: G.B. Pant Engineering College, Ghurdauri, Pauri Garhwal, Uttarakhand, India.
authors.forename: Pranav
authors.initials: P
authors.lastname: Tripathi
authors.affiliation: G.B. Pant Engineering College, Ghurdauri, Pauri Garhwal, Uttarakhand, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Chaudhary
authors.affiliation: G.B. Pant Engineering College, Ghurdauri, Pauri Garhwal, Uttarakhand, India.
authors.forename: Ajeet
authors.initials: A
authors.lastname: Singh
keywords: Chancroid; Haemophilus ducreyi; Molecular docking; Molecular dynamics; RMSD; Rifabutin