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Genomics-guided identification of potential modulators of SARS-CoV-2 entry proteases, TMPRSS2 and Cathepsins B/L.
Prasad, Kartikay; AlOmar, Suliman Yousef; Almuqri, Eman Abdullah; Rudayni, Hassan Ahmed; Kumar, Vijay.
  • Prasad K; Amity Institute of Neuropsychology & Neurosciences (AINN), Amity University, Noida, UP, India.
  • AlOmar SY; Department of College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.
  • Almuqri EA; Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
  • Rudayni HA; Biology Department, College of Science, Imam Muhammad bin Saud Islamic University, Riyadh, Kingdom of Saudi Arabia.
  • Kumar V; Amity Institute of Neuropsychology & Neurosciences (AINN), Amity University, Noida, UP, India.
PLoS One ; 16(8): e0256141, 2021.
Article in English | MEDLINE | ID: covidwho-1362089
ABSTRACT
SARS-CoV-2 requires serine protease, transmembrane serine protease 2 (TMPRSS2), and cysteine proteases, cathepsins B, L (CTSB/L) for entry into host cells. These host proteases activate the spike protein and enable SARS-CoV-2 entry. We herein performed genomic-guided gene set enrichment analysis (GSEA) to identify upstream regulatory elements altering the expression of TMPRSS2 and CTSB/L. Further, medicinal compounds were identified based on their effects on gene expression signatures of the modulators of TMPRSS2 and CTSB/L genes. Using this strategy, estradiol and retinoic acid have been identified as putative SARS-CoV-2 alleviation agents. Next, we analyzed drug-gene and gene-gene interaction networks using 809 human targets of SARS-CoV-2 proteins. The network results indicate that estradiol interacts with 370 (45%) and retinoic acid interacts with 251 (31%) human proteins. Interestingly, a combination of estradiol and retinoic acid interacts with 461 (56%) of human proteins, indicating the therapeutic benefits of drug combination therapy. Finally, molecular docking analysis suggests that both the drugs bind to TMPRSS2 and CTSL with the nanomolar to low micromolar affinity. The results suggest that these drugs can simultaneously target both the entry pathways of SARS-CoV-2 and thus can be considered as a potential treatment option for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Tretinoin / Serine Endopeptidases / Cathepsin B / Genomics / Estradiol / Cathepsin L / SARS-CoV-2 Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0256141

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Tretinoin / Serine Endopeptidases / Cathepsin B / Genomics / Estradiol / Cathepsin L / SARS-CoV-2 Limits: Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Journal.pone.0256141