key: cord-0252426-yyikbmfi
authors: Wang, Zhihan; Guo, Kai; Gao, Pan; Pu, Qinqin; Wu, Min; Li, Changlong; Hur, Junguk
title: Identification of Repurposable Drugs and Adverse Drug Reactions for Various Courses of COVID-19 Based on Single-Cell RNA Sequencing Data
date: 2020-05-16
journal: ArXiv
DOI: nan
sha: 6fd8bb93cc6fa08b2d34682b2357fdc5054d68c1
doc_id: 252426
cord_uid: yyikbmfi

Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. There is no specific drug for COVID-19, highlighting the urgent need for the development of effective therapeutics. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating the gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus. In conclusion, we have identified a list of repurposable anti-SARS-CoV-2 drugs using a systems biology approach.

Baquero-Perez B, Whitehouse A. Hsp70 Isoforms Are Essential for the with 3 technical replicates each. Statistical significance was determined using one-way ANOVA. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Table 1 . A list of potential drugs for treating COVID-19 based on the LINCS database and DEGs between mild and healthy samples in B cells, CD4 + T cells, CD8 + T cells, epithelial cells, NK cells, and macrophages. Connectivity scores were calculated from the CLUE platform. Asterisk (*) represents a clinical trial for its efficacy in COVID-19 disease. (+)

indicates drugs meeting the SC < -90 criteria, while (-) indicates drugs not meeting the criterion. Mebendazole  BRD-K77987382  -+  -+  +  -3  Tubulin inhibitor   Kinetin-riboside  BRD-K94325918  -+  -+  +  -3  Apoptosis stimulant   Nocodazole  BRD-K12539581  -+  -+  +  -3  Tubulin inhibitor   JTC-801  BRD-K17705806  -+  -+  +  -3  Opioid receptor antagonist   Vincristine  BRD-K82109576  --+  +  -+  3  Tubulin inhibitor   Lopinavir  BRD-K99451608  +  ----+  2  HIV protease inhibitor  Phase 4   Ritonavir  BRD-K51485625  +  ----+  2  HIV protease inhibitor  Phase 4   Dexamethasone BRD-A35108200  -+  ----1  Glucocorticoid receptor agonist  Phase 3/4   Niclosamide  BRD-K35960502  ----+  -1  DNA replication inhibitor  Phase 2/3   Lenalidomide  BRD-K05926469  -----+  1  Antineoplastic  Phase 4   Tacrolimus  BRD-K69608737  --+  ---1 Calcineurin inhibitor Phase 3 -K99451608  +  ---+  +  3  HIV protease inhibitor  Phase 4   GW-441756  BRD-K04146668  +  ---+  +  3  Growth factor receptor inhibitor   Treprostinil  BRD-A67438293  +  -+  --+  3  Prostacyclin analog  Tyrphostin-AG-1478  BRD-K68336408  -+  +  -+  -3  EGFR inhibitor   Epoxycholesterol BRD-K61480498  -+  +  +  --3  LXR agonist   Ritonavir  BRD-K51485625  ----+  +  2  HIV protease inhibitor  Phase 4   Hydrocortisone  BRD-A07000685  --+  ---1 Glucocorticoid receptor agonist Phase 3 Linsitinib  BRD-K08589866  +  ---+  +  3  IGF-1 inhibitor   TAK-715  BRD-K52751261  -+  +  --+  3  p38 MAPK inhibitor   Y-27632  BRD-K44084986  -+  +  --+  3  Rho associated kinase inhibitor   AZ-628  BRD-K05804044  --+  +  -+  3  RAF inhibitor   Lestaurtinib  BRD-K23192422  ---+  +  +  3  FLT3 inhibitor   Metformin  BRD-K79602928  --+  ---1  Insulin sensitizer  Phase 3   Atorvastatin  BRD-U88459701  ---+  --1  HMGCR inhibitor  Phase  2/3  Sildenafil  BRD-K50128260  ---+  --1  Phosphodiesterase inhibitor  Phase 3   Verapamil  BRD-A09533288  ---+  --1  Calcium channel blocker  Phase  2/3  Lopinavir  BRD-K99451608  ---+  --1  HIV protease inhibitor  Phase 4   Sildenafil  BRD-K79759585  ---+  --1  Phosphodiesterase inhibitor  Phase  1/2/3  Rosuvastatin BRD-K82941592  ---+  --1  HMGCR inhibitor  Phase 3   Maraviroc  BRD-A04352665  ---+  --1  CC chemokine receptor  antagonist   Phase  1/2   Sitagliptin  BRD-K19416115  ----+  -1 Dipeptidyl peptidase inhibitor **** **** **** **** **** ****

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