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[Preprint]. 2020 Apr 22.
doi: 10.26434/chemrxiv.12153594.

Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2

Tesia Bobrowski  1 , Vinicius M Alves  2 , Cleber C Melo-Filho  1 , Daniel Korn  1   3 , Scott Auerbach  4 , Charles Schmitt  2 , Eugene N Muratov  1 , Alexander Tropsha  1
Affiliations

Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2

Tesia Bobrowski et al. ChemRxiv. .

Update in

Abstract

The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation.<br>.

Keywords: CoVID-19; DrugBank molecules; QSAR Modeling; SARS-CoV-2; coronavirus; virtual screening.

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Conflict of interest statement

The authors declare no actual or potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Study design.
Figure 2.
Figure 2.
Alignment of SARS-CoV and SARS-CoV-2 Mpro monomers. (a) Primary sequence alignment highlighting the conserved residues in bold font. The binding site residues are shown in red and the catalytic dyad, represented by His41 and Cys145, is marked with asterisks. (b) Alignment of Mpro monomers available in PDB (IDs: 5N19, 6LU7). (c) Visualization of the overlap between residues at the Mpro active site for SARS and SARS-CoV-2. The red dashed circles show the conserved catalytic dyad and the remarkable conservation of the binding site of Mpro between the coronaviruses.
Figure 3.
Figure 3.
Receiver operating characteristic (ROC) after running the docking validation screening with known inhibitors and non-inhibitors of Mpro.
See this image and copyright information in PMC

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