Molecular Docking and Identification of Candidate Blockers for Endonuclease Domain of Lassa Virus Polymerase as Potential Drugs

Abstract

Lassa fever is a deadly hemorrhagic disease virus caused by Lassa virus (LASV) which is a member of the Arenaviridae virus family. Lassa virus-encoded L polymerase is required for the replication and transcription of the RNA virus. There is no available vaccine as ribavirin remains the only treatment provided it is administered in the early stages of infection. This study aims at searching for possible durg candidates that can compare favourably well with ribavirin or possibly exhibit a better potency against the virus. The computational modeling method of docking was performed with AutoDock 4.2. Bioavailability test and Toxicological prediction using Swiss ADME, Toxtree version 2.6.6 and pkCSM softwares. The result obtained from this investigation revealed that some of the selected inhibitors considered in this investigation such as α pinene, β pinene, limonene, monoterpene, 6-gingerol showed binding energy of -4.32 kcalmol^-1, -4.30 kcalmol^-1, -4.25 kcalmol^-1, -3.87 kcalmol^-1 and - 3.48 kcalmol^-1 respectively compete favouarably with that of ribavirin (-4.39kalmol-1) which was considered as standard while the inhibition constant (Ki) of the interaction between the target and that α pinene (681.86 µM), β pinene (768.90 µM) and limonene(706.53 µM) was low when compared others except for ribavirin. The ADME analysis (Lipinski’s rule) of the selected Inhibitors predicted all the investigated inhibitors satisfied the Lipinski’s rule. It was discovered that the toxicity prediction of selected inhibitors using Toxtree and pkCSM showed that they are less toxic and considered safe for usage. This study, therefore, reveals that α pinene, β pinene, limonene promises to be a possible drug candidate as it has the inhibitory potential against Lassa virus L polymerase comparable to ribavirin, bioavailable and less toxic.