Medicinal and Environmental Chemistry: Experimental Advances and Simulations (Part II)

Novel Drug Development Strategies- A Case Study With SARS-CoV-2

Author(s): Iqbal Azad*, Tahmeena Khan, Mohammad Irfan Azad and Abdul Rahman Khan

Pp: 238-267 (30)

Doi: 10.2174/9789814998307121010014

* (Excluding Mailing and Handling)


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.

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