The current epidemic of Severe Acute Respiratory Syndrome coronavirus
(SARS-CoV-2) has led to a major health crisis in 2020. SARS-CoV-2 has spike
protein, polyproteins, nucleoproteins, and membrane proteins with RNA polymerase,
3-chymotrypsin-like protease, papain-like protease, helicase, glycoprotein, and
accessory proteins. These are probable targets to be explored for the discovery of
antiviral agents, still, to date, no definite treatment or vaccine has been discovered.
Virtual screening with molecular docking has its advantage to speed up the drug
development procedure in an accurate manner. In this chapter, novel computational
strategies for drug discovery have been elaborated. Docking tools and drug filtering
rules which may efficiently assist the drug development procedure and channelize the
whole process in the right direction have also been discussed. A case study with 322
natural, semi-synthetic, and synthetic derivatives of citric acid (2-hydroxy-1,2-
3-propane tricarboxylic acid), in search of a potential lead molecule to combat the
novel coronavirus SARS-CoV-2, has been elaborated. The derivatives were explored
from the PubChem database. The obtained library of compounds was filtered through
Lipinski’s rules, out of which, 74 obeyed the rule and were further subjected to
molecular docking investigation against the SARS-CoV-2 replicase polyprotein 1a or
pp1a (ID: 6LU7), with AutoDock Vina and iGEMDOCK. Deptropine possessed the
highest binding affinity, in terms of released binding energy (-7.4 kcal/mol), against the
SARS-CoV-2 replicase polyprotein 1a.
Keywords: Citric acid, Computational strategies, Drug, Docking, Repurposing,
SARS-CoV-2, Virtual screening.