Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis

Abstract

Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness. This illness is spurred on by a coronavirus known as SARS-associated coronavirus (SARS-CoV). SARS was first detected in Asia in late February 2003. The genome of this virus is very similar to the SARS-CoV-2. Therefore, the study of SARS-CoV disease and the identification of effective drugs to treat this disease can be new clues for the treatment of SARS-Cov-2. This study aimed to discover novel potential drugs for SARS-CoV disease in order to treating SARS-Cov-2 disease based on a novel systems biology approach. To this end, gene co-expression network analysis was applied. First, the gene co-expression network was reconstructed for 1441 genes, and then two gene modules were discovered as significant modules. Next, a list of miRNAs and transcription factors that target gene co-expression modules' genes were gathered from the valid databases, and two sub-networks formed of transcription factors and miRNAs were established. Afterward, the list of the drugs targeting obtained sub-networks' genes was retrieved from the DGIDb database, and two drug-gene and drug-TF interaction networks were reconstructed. Finally, after conducting different network analyses, we proposed five drugs, including FLUOROURACIL, CISPLATIN, SIROLIMUS, CYCLOPHOSPHAMIDE, and METHYLDOPA, as candidate drugs for SARS-CoV-2 coronavirus treatment. Moreover, ten miRNAs including miR-193b, miR-192, miR-215, miR-34a, miR-16, miR-16, miR-92a, miR-30a, miR-7, and miR-26b were found to be significant miRNAs in treating SARS-CoV-2 coronavirus.

A comprehensive review of artificial intelligence and network based approaches to drug repurposing in Covid-19

“… Title Datasets used Repurposed Drugs Evaluation Criteria Tools used Ref. 1 Designing a Network Proximity-Based Drug Repurposing Strategy for COVID-19 BioGRID – Network proximity/ Network Diffusion Cytoscape, VarElect tool [169] 2 Network medicine framework for identifying drug-repurposing opportunities for COVID-19 13 Datasets, DrugBank, STRING 989 Drugs, 77 Validated in VeroE6 Cells, 76/77 validated in Human Cells Network proximity, network diffusion, Network AI Experimental, Ensembl algorithmic prediction [176] 3 Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis DGIDb, gene co-expression, DrugBank 5 Drugs Gene enrichment analysis for Genes and miRNA Node degree and centralities [195] 4 Network-based repurposing identifies anti-alarmins as drug candidates to control severe lung inflammation in COVID-19 Uniprot, STRING, CMap, LINCS, GEO – Gene expression profiling CMap ranking [184] 5 Integrative In Silico Investigation Reveals the Host-Virus Interactions in Repurposed Drugs Against SARS-CoV-2 STITCH, KEGG, BioGRID, PubChem, IID, – Enrichment analysis, Molecular docking DAVID, GOplot, AutoDock Vina, Cytoscape, Ligplot+ [196] 6 Discovery of Potential Therapeutic Drugs for COVID-19 Through Logistic Matrix Factorization with Kernel Diffusion – 4 Drugs 5-fold cross validations, AUC, AUPRs, recall, similarity diffusion Molecular docking [197] 7 HeTDR: Drug repositioning based on heterogeneous networks and text mining Mesh, DrugBank, PubMed 10 Drugs AUPR, AUROC, F1-measure – [198] 8 ...…”

“…There are multiple significant studies utilizing this approach to repurpose the drugs in Covid-19 and other diseases. Once recent Covid-19 based drug repurposing study is done in [195] where gene co-expression-based network for 1441 genes was constructed and analysis was performed. The analysis resulted in two significant gene co-expression network modules and then data related to miRNAs and transcription factors targeting co-expressed modules’ genes were gathered from reputable databases led to the establishment of two subnetworks consisted of transcription factors and miRNAs.…”

Drug repurposing for identification of potential spike inhibitors for SARS-CoV-2 using molecular docking and molecular dynamics simulations

“…The outbreak of SARS-CoV-2 spawned multiple analyses where the goal was to select substances that can be useful in COVID-19 treatment. Most of the studies apply a drug repurposing strategy that identifies new therapeutics from already approved substances, since de novo identification of drugs is a costly and lengthy process [28] . In one of the research studies, it was found that emodin, omipalisib, and tipifarnib can serve as inhibitors of RdRp [26] .…”

“…Another docking study revealed that the drugs cytarabin, raltitrexed, tenofovir, cidofovir, lamivudine and fludarabine are potent binders of the spike protein [30] . In other research, rather than finding specific protein targets, the authors analyzed gene-interaction networks and found several potential drugs including fluorouracil, cisplatin, sirolimus, cyclophosphamide, and methyldopa [28] . Several other drugs such as chloroquine, hydroxychloroquine, remdesivir, galidesivir and others were also considered for potential treatment of COVID-19 patients [31] .…”

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug–gene interaction networks analysis

“…Drug repositioning is also referred to as drug repurposing, drug therapeutic, drug recycling, and drug reprofiling 13 , 14 . There are usually three kinds of methods for drug repurposing, including experimental biological methods, computational methods, and mixed methods 10 , 15 , 16 . Computational methods can be referred to as molecular docking, network mapping, signature matching, genetic association, and retrospective clinical analysis 13 , 17 , 18 .…”