4. Conclusion
The biggest challenge in battling the novel coronavirus (nCoV-19)
pandemic is the dearth of effective therapeutic regimens. The presentin silico study was aimed to assess the probable utility of
bioactive compounds, 2-deoxy-D-glucose and its derivative
1,3,4,6-Tetra-O-acetyl-2-deoxy-D-glucopyranose against nCoV-19. The most
pertinent viral physiological targets (viral spike glycoprotein S2,
viral NSP15 endoribonuclease and viral main protease 3CLpro) were
selected as receptors for conducting molecular docking analysis. The
computer based pharmacophore modeling approach has generated interesting
insights into the underlying binding mechanisms of the above-mentioned
viral receptors with 2-DG and 2-DG derivative. It is noteworthy that
2-deoxy-D-glucose have shown significant activity towards inactivating
the SARS-CoV-2 viral receptors, wherein, the E-value of docking of 2-DG
with viral main protease 3CLpro and NSP15 endoribonuclease is
significantly better than that of the standard drug lopinavir and
favipiravir. Such significant binding affinities of 2-DG result from
formation of a salt bridge between the hydroxyl group of
2-deoxy-D-glucose and carbonyl residue of Proline
(108th position) found in the viral protease.
Similarly, 2-DG tetra-acetate glucopyranose derivative (prodrug of 2-DG)
displayed exceptional binding efficiencies while docking with viral
protease, viral endonuclease and spike glycoprotein. The in
silico bioactivity analysis suggest that both these molecules act
mainly as protease inhibitors. Present results also indicate that both
2-DG and 2-DG derivative possess adequate oral bioavailability without
any major signs of toxicity or side effects,
In sum, present in silico results, taken together with the
published empirical findings on the effects of 2-DG on retrovirus
infected cell lines and murine model systems, suggest that 2-DG may
considerably reduce the infectivity and virulence of nCOVID-19 by
inhibiting both the entry and the replication of the virus inside the
host cells. To verify this possibility, further basic studies on model
systems infected with nCOVID-19 are necessary before human clinical
trials can be conducted. In view of the huge global devastation caused
by the current viral pandemic and lack of any effective therapy,
research work to explore the therapeutic potential of 2-deoxy-D-glucose
and 1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose should be urgently
undertaken with well coordinated multi-institutional collaborations.