Discovering Candidates For COVID-19 Treatment With Virtual Drug Screening Technology

The University Department of Chemical & Biomolecular Engineering Distinguished Professor Lee Sang-yeob (Vice President Research) and South Korea co-researchers Dr. Pasteur Institute gimseungtaek a ' drug corona using virtual screening techniques 19 developing drugs ' has succeeded in eight said one.

The findings of the international journal " National Academy of Sciences Newsletter (PNAS), the 7 Mon. 7 days been posted online.

• Paper title: Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay
• About the author: Lee Sang-yeob (Korea Advanced Institute of Science and Technology, Corresponding Author), gimseungtaek (Institut Pasteur Korea, corresponding author), Chapter flyer (Korea Advanced Institute of Science and Technology, the first author), phase inversion is (Institut Pasteur Korea, the second author), including the total 4 people

Coronavirus Infectious Disease- 19 (hereinafter referred to as Corona 19) is developing as a global pandemic and currently seriously threatens human health. Corona 19 Treatment The US Food and Drug Administration for the purpose of (FDA) received formal approval from Harlem Pradesh Birr (trade name Vespa keulreori) is still open. However, your current clinical, the recovery period does not mortality was reduced 5 to a treatment effect expected by reducing the degree days It is known that it does not reach. Also, since remdesivir is an intravenous drug, it has to be administered for several days through hospitalization at a medical institution, so it is not suitable for a pandemic situation. Therefore, there was an urgent need to develop an oral treatment that dramatically reduces the death rate due to COVID- 19 and shortens the treatment period.

The Lee Sang-yeob Distinguished Professor and co-researchers Dr. Institute Pasteur Korea gimseungtaek Corona is a drug re-creation strategy using a virtual drug screening technology 19 conducted a drug research and development.

The research team established a drug re-creation strategy using virtual screening technology for rapid development of therapeutic agents in response to the pandemic situation. Drug reinvention is a method of finding new indications for FDA- approved drugs that have already been tested for safety or drugs in clinical trials. This strategy can shorten the time required for the drug development process, making it a new drug development strategy suitable for a pandemic situation such as COVID- 19.

Dr. Woo-Dae Jang of the Department of Biochemical Engineering at our university first built a virtual library of 6,218 drugs by collecting FDA- approved drugs or drugs in clinical trials from the database. Since it is time-consuming and expensive to verify all these drugs in an experiment, we introduced a computer-based virtual screening technology that can rapidly select only promising drugs as antiviral drugs.

The existing docking simulation-based virtual screening technology had a problem in that the hit rate of active substances was very low due to a high false positive rate. The research team succeeded in increasing the accuracy of virtual screening by introducing the structural similarity analysis module and the interaction similarity analysis module before and after docking. The virtual screening technology developed through this research is characterized by being able to quickly and accurately screen various candidate drugs using protein - drug complex structure information.

The research team also developed an algorithm to automatically generate active structures for prodrugs based on nucleotide analogues, which are mainly used as antiviral drugs. Prodrugs have no medicinal effect by themselves and show medicinal effects only when converted into an active structure through body metabolism. Therefore, it is important to perform docking simulation after structural transformation of prodrugs into active form. The team succeeded to automatically generate the active form of the structure of different nucleic acid analogs, including the Harlem-based prodrug Pradesh Vir, could improve the accuracy of docking simulations.

Researchers in virtual screening platform SARS - coronavirus -2 (SARS-CoV-2) of the clone and to play an essential role in the proliferation protease (3CL hydrolase, Mpro) and RNA polymerase (RNA-dependent RNA polymerase, RdRp) were selected into 15 and 23 candidate compounds, respectively.

Then, the virtual screening to screening 38 of the species biological safety of Institut Pasteur Korea for drugs three grades (BSL-3) had the advantage of proven image-based cellular antiviral activity in the laboratory analysis platform efficacy.

First, SARS - coronavirus -2 monkeys infected kidney cells (Vero cell) in vitro with (in vitro) results of the experiment, 38 of the species of the drug seven antiviral activity in the species of the drug was confirmed.

In addition, the verification 7 human lung cells for the drug species (Calu-3 cell) were performed to further validate the experiment at 3 has been confirmed the antiviral activity in the species of the drug. Candidate drug, cancer and idiopathic pulmonary fibrosis (idiopathic pulmonary fibrosis) in ten Omi Parliament being clinical progress (omipalisib), cancer and progeroid syndromes (progeria) Tea being clinical advances to the FIFA nip (tipifarnib), a clinically as anticancer drugs as plant extracts There is an emodin in progress. In particular, Omifalisib has been confirmed to have about 200 times higher antiviral activity than remdesivir, the current standard treatment for COVID- 19, and tipipanib has been confirmed to have antiviral activity at a level similar to that of remdesivir.

Drugs whose antiviral effects have been confirmed at the cellular level require preclinical testing using virus-infected animal models. Accordingly, the research team evaluated the efficacy of one of the candidate drugs through the Ministry of Science and ICT's preclinical support project for corona treatment. However, drug toxicity to animals was observed during this process. Additional preclinical trials will be conducted to find the optimal drug concentration that can reach a therapeutically effective concentration while minimizing the toxicity of the drug. In addition, preclinical trials are planned for the remaining candidate drugs.

An official from the research team explained that through this study, a virtual drug screening platform with excellent predictive performance was built, and through this, promising candidates for the treatment of COVID- 19 could be found in a short time.

Lee Sang-yeob Distinguished Professor " Through this research and the significance in having that laid the foundation technology that can respond quickly when new viruses emerge, a technology that can be applied even when a similar virus, a new virus emerge in them through the next corona virus family We want to develop” he said.

Meanwhile, this research was carried out with the support of the KAIST Corona Response Science and Technology New Deal Project and the Bio / Medical Technology Development Project supported by the Ministry of Science and ICT.