Preprint Hypothesis Version 2 Preserved in Portico This version is not peer-reviewed

Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach

Version 1 : Received: 2 March 2020 / Approved: 3 March 2020 / Online: 3 March 2020 (11:41:51 CET)
Version 2 : Received: 20 March 2020 / Approved: 23 March 2020 / Online: 23 March 2020 (10:19:17 CET)

How to cite: Senathilake, K.; Samarakoon, S.; Tennekoon, K. Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach. Preprints 2020, 2020030042 (doi: 10.20944/preprints202003.0042.v2). Senathilake, K.; Samarakoon, S.; Tennekoon, K. Virtual Screening of Inhibitors Against Spike Glycoprotein of SARS-CoV-2: A Drug Repurposing Approach. Preprints 2020, 2020030042 (doi: 10.20944/preprints202003.0042.v2).

Abstract

The novel coronavirus (SARS-CoV-2) is a human pathogen recently emerged in China, causing a global pandemic of severe respiratory illness (COVID19). SARS-CoV-2 makes entry into human cells through its spike (S) protein that binds to cell surface receptors. Widespread of SARS-CoV-2 has been attributed to high affinity of S protein to its receptor. A homology model of the receptor binding domain of SARS-CoV-2 S protein (RBD) was built. RBD- receptor docking and published molecular dynamics data were used to map the key RBD-receptor interaction hotspot (RBDhp) on the RBD. Primary virtual screening was carried out against RBDhp using more than 3300 compounds approved by U.S Food and Drug Administration (FDA) and other authorities for human use. Compounds that bind to hpRBD with a binding energy ≤ - 6.5 kcal/mol were subjected to secondary screening using a recently published cryo EM (2.9 Å) structure of RBD. A cardiac glycoside (dgitoxin), two anthracyclines (zorubicin and aclarubicin), a tetracycline derivative (rolitetracycline), a cephalosporin (cefoperazone) and a food dye (E-155) were predicted to be most potent inhibitors of RBD – receptor interaction. An anti-asthmatic drug (zafirlukast) and several other drugs (itrazol, fazadinium, troglitazone, gliquidone, Idarubicin, Oxacillin) were found to be high affinity binders that may have a potential to inhibit RBD – receptor interaction.

Subject Areas

Flue; Virus; COVID19; SARS CoV-2; Spike Protein; Virtual Screening; dgitoxin; anthracycline; rolitetracycline; E-155

Comments (1)

Comment 1
Received: 23 March 2020
Commenter: Sameera Samarakoon
Commenter's Conflict of Interests: Author
Comment: 1.) In the topic - 2019 Novel Corona Virus changed to its official name SARS-CoV-2 2.) We carried out the second round of virtual screening using new high-resolution Cryo-EM structure which was not available at the time of submitting the initial version of the current manuscript. these new data and their detailed analysis were included in the manuscript. 3.) The manuscript was reformatted according to the submission guidelines of post publish peer-review journal - Sci
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