Korean J Fam Pract.  2021 Aug;11(4):312-321. 10.21215/kjfp.2021.11.4.312.

Recurrent Neural Network Based Drug Repurposing to Address SARS-CoV-2 (COVID-19), and the in vitro Antiviral Efficacy of Peroxisome Proliferator-Activated Receptors-Gamma Agonist

• Kim NH
• Dong JJ

• KMID: 2519286
• DOI: http://doi.org/10.21215/kjfp.2021.11.4.312

Abstract

Background
Acute respiratory distress syndrome resulting from coronavirus (COVID-19) infection is triggered by cytokine storms, so activation of inhibitory modulators of inflammatory pathways has become a new candidate modality for COVID-19 treatment. This study utilized artificial intelligence (A.I.) to search databases, and compiled a list of 50 drugs deemed plausible candidates for COVID-19 treatment. We then designed a cellbased in vitro assay to evaluate the efficacy of PPAR-γ agonists against viral induced inflammation.
Methods
We applied RNN screening to Drugbank and CORD-19 databases, and selected as the top 50 drug candidates those compounds that have the highest docking energy with the main protease produced by SARS-CoV-2 infected cells. We then designed an in vitro study including chloroquine, lopinavir, and remdesivir treated cells as controls, and cells treated with two PPAR-γ agonists as experimental groups. SARS-CoV-2 infected cells were administered a range of concentrations of each drug, and inhibition-normalized infection ratios were derived using an immunofluorescence method.
Results
The positive control groups’ SI’s were >1 (chloroquine SI=9.28, remdesivir SI=4.56, lopinavir SI=3.5), confirming their inhibitory effects against SARS-CoV-2 infection. However, chloroquine and lopinavir displayed high cytotoxicity, and Remdesivir displayed low cytotoxicity. The two PPAR-γ agonist SIs indicated that they possess no inhibitory effect against SARS-CoV-2 infection, but are clinically safe.
Conclusion
The PPAR-γ agonists did not reduce numbers of SARS-CoV-2 infected cells. Nevertheless, this study has significance in that we introduced the use of A.I. for rapid new drug development during the COVID pandemic.

Keyword

COVID-19; Artificial Intelligence; Peroxisome Proliferator-Activated Receptors; in vitro