AUTHOR=Yu Wenhui , Bai Yuxin , Raha Arjun , Su Zhi , Geng Fei TITLE=Integrative In Silico Investigation Reveals the Host-Virus Interactions in Repurposed Drugs Against SARS-CoV-2 JOURNAL=Frontiers in Bioinformatics VOLUME=1 YEAR=2022 URL=https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2021.763540 DOI=10.3389/fbinf.2021.763540 ISSN=2673-7647 ABSTRACT=

The ongoing COVID-19 outbreak have posed a significant threat to public health worldwide. Recently Toll-like receptor (TLR) has been proposed to be the drug target of SARS-CoV-2 treatment, the specificity and efficacy of such treatments remain unknown. In the present study we performed the investigation of repurposed drugs via a framework comprising of Search Tool for Interacting Chemicals (STITCH), Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking, and virus-host-drug interactome mapping. Chloroquine (CQ) and hydroxychloroquine (HCQ) were utilized as probes to explore the interaction network that is linked to SARS-CoV-2. 47 drug targets were shown to be overlapped with SARS-CoV-2 network and were enriched in TLR signaling pathway. Molecular docking analysis and molecular dynamics simulation determined the direct binding affinity of TLR9 to CQ and HCQ. Furthermore, we established SARS-CoV-2-human-drug protein interaction map and identified the axis of TLR9-ERC1-Nsp13 and TLR9-RIPK1-Nsp12. Therefore, the elucidation of the interactions of SARS-CoV-2 with TLR9 axis will not only provide pivotal insights into SARS-CoV-2 infection and pathogenesis but also improve the treatment against COVID-19.