Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates
A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3.
Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives.
The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.
The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.
“We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST.
“The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee.
This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326).
KAIST is the first and top science and technology university in Korea. KAIST was established in 1971 by the Korean government to educate scientists and engineers committed to industrialization and economic growth in Korea.
Since then, KAIST and its 67,000 graduates have been the gateway to advanced science and technology, innovation, and entrepreneurship. KAIST has emerged as one of the most innovative universities with more than 10,000 students enrolled in five colleges and seven schools including 1,039 international students from 90 countries.
On the precipice of its semi-centennial anniversary in 2021, KAIST continues to strive to make the world better through its pursuits in education, research, entrepreneurship, and globalization. For more information about KAIST, please visit http://www.
-About Institut Pasteur Korea
Institut Pasteur Korea (IPK) is a non-profit research institute established in 2004 as part of the scientific cooperation between the Rep. of Korea and France, focusing on infectious diseases. Utilizing its core research capabilities, cell- and image-based screening platforms, to understand disease mechanisms and accelerate the development of new treatments, IPK contributes to addressing unmet global health issues, including emerging infectious diseases such as COVID-19, MERS, Zika fever, viral hepatitis, tuberculosis, antibiotic resistance, cancer, and neglected diseases.
By providing fundamental technologies to bridge Korean and international bio-pharma science and promote multi-disciplinary projects globally, IPK stands at the forefront of drug discovery research contributing to Korea’s scientific, intellectual, and technical resources as well as its global infectious disease preparedness and response. IPK is an integral member of the Institut Pasteur International Network (IPIN), consisting of 33 members located in 25 countries. (http://www.
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