3.5 Bioactivity analysis
Molinspiration was used to virtually screen the biological activity of drug moieties, per say 2-DG and 2-DG derivative in the present study. The fundamental principle behind this in silico bioactivity screening is the identification of substructure(s) responsible for endowing pharmacological features (GPCR binding ability, ion channel modulation potential, kinase inhibition activity, nuclear receptor binding potential, and protease inhibition) to the drug molecules being studied. The bioactivity score of the ligands and standard chemosynthetic moieties is presented in Table 4 . In general, if the bioactivity score for a particular target is more than 0.0, then the said drug moiety is considered to be highly active. Additionally, a bioactivity score of a ligand lying between -5.0 and 0.0 is considered to be moderately active. However, bioactivity scores of ligands below -5.0 render it to be inactive (Singh et al., 2013). As observed in Table 4, the bioactivity scores of 2-DG for most of the bioactivity descriptors were below -0.5, thereby indicating its inactivity towards those targets. However, 2-DG possessed moderate bioactivity as ion channel modulator (Bioactivity score Ion channel modulator ~ -0.14) and protease inhibitor (Bioactivity score Protease inhibitor ~ -0.37). This bioactivity score of 2-DG is in corroboration with the molecular docking results which also suggest 2-DG to be a significant protease inhibitor (E 2-DG + Protease = -140.05 Kcal/mol). The antiviral effect of 2-DG has also been recognized in previous studies. Inhibition of multiplication has been reported for some enveloped viruses such as influenza virus, sindbis virus, semliki forest virus, herpes simplex virus, respiratory syncytial virus and measles virus (Kang & Hwang, 2006; Krol et al., 2017). Furthermore, 2-DG eliminated genital herpes from most of the tested patients. It also alleviated the severity of infection of calves with respiratory syncytial virus and infectious of bovine rhino-tracheitis virus (Leung et al., 2012). According to all these earlier studies, inhibition of viral envelope biosynthesis and virion assembly due to blocked glycosylation of membrane proteins appears to be the major mechanism of 2-DG for virus attenuation. This has been supported by altered gel electrophoresis profiles of membrane proteins as well as denuded appearance of budding particles shown by electron microscopy. Studies also suggest that 2- DG can also suppress viral gene expression or viral replication (Camarasa et al., 1986; Kang & Hwang, 2006; Leung et al., 2012; Krol et al., 2017).
Furthermore, the bioactivity score of 2-DG derivative (1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose) suggested that it mainly acts as a GPCR ligand (Bioactivity score GPCR ligand~ 0.13), ion channel modulator (Bioactivity scoreIon channel modulator ~ 0.04) and protease inhibitor (Bioactivity score Protease inhibitor~ 0.17). In alliance with the bioactivity analysis, molecular docking data of 2-DG derivative has also suggested it to be a significant protease inhibitor (E 2-DG derivative + Protease = -187.64 Kcal/mol).