ICBCB2020 1 Repurposing drugs for targetting SARS-Cov-2 in Panel discussion: Advances in Bioinformatics and their Impact on Healthcare in ICBCB2020 Y-h. Taguchi, Department of Physics, Chuo University 17th May, 2020.

ICBCB2020 2 Because of rapid spread of SARS-CoV-2 infection world wide, it is important to invent some effective drug for this virus. But how? But how? Repurposing the known drug Repurposing the known drug Drug discovery from scratch will take more than 10 years. We cannot wait for so long. But repurposing can be performed more quickly, since adverse effects have already been reported. In addition to this, there are pretty number of known anti-viral drugs! At least, there are as many as 1170 hits of “repurposing” and “SARS-CoV-2”, 296 hits of “repositioning” and “SARS-CoV-2” in google scholar.

ICBCB2020 3 In silico drug discovery (DD) is effective method to accelerate repurposing drugs, because …. Low cost Pre-screening before expensive and time consuming wet experiments Can screen many drug candicate Two main brunch of in silico DD Ligand based DD (LBDD): Screen drugs based upon the similarity between known drugs and new drug candidate compounds Structure based DD (SBDD): Screen drugs thorough docking simulation between drug compounds and target protein

ICBCB2020 4 LBDD: Need the knowledge about known drug → Not applicable to SARS-CoV-2, since no known drugs for SARS-CoV-2. SBDD: Need known protein structure → not known for SARS- CoV-2, must be computationally predicted. https://gendai.ismedia.jp/articles/-/72229?page=3 Is the structure predicted true? AVIGAN developed and manufactured by Japanese Company,Toyama Chemical.

ICBCB2020 5 The third approach: Screening drug through analyzing gene expression profiles altered by infection Gene expression SARS-CoV-2 infection Drug treatment If up/downregulation is reversed, this can be possible drugs.

ICBCB2020 6 I have already I have already published two published two preprints, preprints, in silico in silico DD DD using gene using gene expression expression

ICBCB2020 7 Term Overlap P-value Adjusted P-value Ivermectin-7.5 mg/kg in CMC-Rat-Liver-1d-dn 12/277 2.98E-06 9.93E-06 Ivermectin-7.5 mg/kg in CMC-Rat-Liver-5d-dn 12/289 4.60E-06 1.44E-05 Ivermectin-7.5 mg/kg in CMC-Rat-Liver-3d-dn 11/285 2.29E-05 5.56E-05 Ivermectin-7.5 mg/kg in CMC-Rat-Liver-1d-up 10/323 3.28E-04 5.39E-04 Ivermectin-7.5 mg/kg in CMC-Rat-Liver-5d-up 8/311 4.06E-03 5.10E-03 Ivermectin-7.5 mg/kg in CMC-Rat-Liver-3d-up 8/315 4.38E-03 5.46E-03 In our second preprint, ivermectin ivermectin was one of hits! DrugMatrix in Enrichr Enrichr https://asia.nikkei.com/Spotlight/Coronavirus/Parasite-killing-drug-ivermectin-heads-into-coronavirus-trials Originally, discovered by Japanese Prof. Omura, Novel prize winner.

ICBCB2020 8 Cloud intelligence for drug repurposing toward SARS-CoV-2 Cloud intelligence for drug repurposing toward SARS-CoV-2 https://amp.pharm.mssm.edu/covid19/ https://amp.pharm.mssm.edu/covid19/

ICBCB2020 9 Conclusions Repurposing drugs with targeting SARS-CoV-2 is a good opportunity to demonstrate the usefulness of Bioinformatics that can attack “real” problem! Huge number of SBDD, LBDD and gene expression based DD have been proposed. Cloud intelligence has started to be effective. In near future, bioinfomatics will be not negligible tools for repurposing drugs toward the various diseases, including those targeting pandemic.