Identifying Drug Candidates for COVID-19 with Large-Scale Drug Screening

Yifei Wu; Scott D Pegan; David Crich; Lei Lou; Lauren Nicole Mullininx; Edward B Starling; Carson Booth; Andrew Edward Chishom; Kuan Y Chang; Zhong-Ru Xie

doi:10.3390/ijms24054397

Identifying Drug Candidates for COVID-19 with Large-Scale Drug Screening

Int J Mol Sci. 2023 Feb 23;24(5):4397. doi: 10.3390/ijms24054397.

Authors

Yifei Wu¹, Scott D Pegan², David Crich³, Lei Lou¹, Lauren Nicole Mullininx^{1

4}, Edward B Starling^{1

4}, Carson Booth^{1

4}, Andrew Edward Chishom^{1

4}, Kuan Y Chang⁵, Zhong-Ru Xie¹

Affiliations

¹ School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA.
² Division of Biomedical Sciences, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
³ Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
⁴ Franklin College of Arts and Sciences, University of Georgia, Athens, GA 30602, USA.
⁵ Department of Computer Science and Engineering, National Taiwan Ocean University, Keelung 202, Taiwan.

Abstract

Papain-like protease (PL^pro) is critical to COVID-19 infection. Therefore, it is a significant target protein for drug development. We virtually screened a 26,193 compound library against the PL^pro of SARS-CoV-2 and identified several drug candidates with convincing binding affinities. The three best compounds all had better estimated binding energy than those of the drug candidates proposed in previous studies. By analyzing the docking results for the drug candidates identified in this and previous studies, we demonstrate that the critical interactions between the compounds and PL^pro proposed by the computational approaches are consistent with those proposed by the biological experiments. In addition, the predicted binding energies of the compounds in the dataset showed a similar trend as their IC₅₀ values. The predicted ADME and drug-likeness properties also suggested that these identified compounds can be used for COVID-19 treatment.

Keywords: COVID-19; MD simulations; PL protease; drug discovery; virtual screening.

MeSH terms

Antiviral Agents
COVID-19 Drug Treatment
COVID-19*
Drug Evaluation, Preclinical
Humans
Molecular Docking Simulation
Molecular Dynamics Simulation
Papain
Protease Inhibitors
SARS-CoV-2

Substances

Papain
Protease Inhibitors
Antiviral Agents

Grants and funding

In this research, Y.W., L.L., and Z.-R.X. were supported by a faculty seed grant (2231464F22) from the University of Georgia and K.Y.C. was supported by the Ministry of Science and Technology, R.O.C., under MOST-108-2221-E-019-052.