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).