The SARS-CoV-2 helicase as a target for antiviral therapy: Identification of potential small molecule inhibitors by in silico modelling

Pitsillou, Eleni; Liang, Julia; Hung, Andrew; Karagiannis, Tom C.

doi:10.1016/j.jmgm.2022.108193

Cited by 9 publications

(5 citation statements)

References 85 publications

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“…The binding site of the SARS-COV-2 helicase (NSP13) is located between the 1A and 2A domains, comprising important amino acids necessary for ATP binding; Asp374, Glu375, Ser377, Asp401, Gln404, Arg443, Lys288, Ser289, Arg567, and Gly538 (PDB ID: 5RLG ). Experimental and in-silico studies have also been reported targeting the helicase with different molecules [ [106] , [107] , [108] , [109] , [110] , [111] ]. We docked the fortunellin into the active site of the SARS-CoV-2 helicase and found that it achieved a better docking score of −9.8 kcal/mol than the re-docked co-crystallized ligand.…”

Section: Discussionmentioning

confidence: 99%

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host

Agrawal

Pathak

Mishra

et al. 2022

Computers in Biology and Medicine

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Section: Discussionmentioning

confidence: 99%

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host

Agrawal

Pathak

Mishra

et al. 2022

Computers in Biology and Medicine

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“…Relatively little is known about recQ4 other than its important role in genetic stability. Other helicases besides recQ4 have been suggested as potential therapies for COVID-19 based on their antiviral activity [ 105 ]. HCF1 —HCF1 is involved in control of the cell cycle and has regulatory roles in a multitude of processes related to transcription.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Kartchner,

McCoy,

Dubey

et al. 2023

Biology

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Multiple studies have reported new or exacerbated persistent or resistant hypertension in patients previously infected with COVID-19. We used literature-based discovery to identify and prioritize multi-scalar explanatory biology that relates resistant hypertension to COVID-19. Cross-domain text mining of 33+ million PubMed articles within a comprehensive knowledge graph was performed using SemNet 2.0. Unsupervised rank aggregation determined which concepts were most relevant utilizing the normalized HeteSim score. A series of simulations identified concepts directly related to COVID-19 and resistant hypertension or connected via one of three renin–angiotensin–aldosterone system hub nodes (mineralocorticoid receptor, epithelial sodium channel, angiotensin I receptor). The top-ranking concepts relating COVID-19 to resistant hypertension included: cGMP-dependent protein kinase II, MAP3K1, haspin, ral guanine nucleotide exchange factor, N-(3-Oxododecanoyl)-L-homoserine lactone, aspartic endopeptidases, metabotropic glutamate receptors, choline-phosphate cytidylyltransferase, protein tyrosine phosphatase, tat genes, MAP3K10, uridine kinase, dicer enzyme, CMD1B, USP17L2, FLNA, exportin 5, somatotropin releasing hormone, beta-melanocyte stimulating hormone, pegylated leptin, beta-lipoprotein, corticotropin, growth hormone-releasing peptide 2, pro-opiomelanocortin, alpha-melanocyte stimulating hormone, prolactin, thyroid hormone, poly-beta-hydroxybutyrate depolymerase, CR 1392, BCR-ABL fusion gene, high density lipoprotein sphingomyelin, pregnancy-associated murine protein 1, recQ4 helicase, immunoglobulin heavy chain variable domain, aglycotransferrin, host cell factor C1, ATP6V0D1, imipramine demethylase, TRIM40, H3C2 gene, COL1A1+COL1A2 gene, QARS gene, VPS54, TPM2, MPST, EXOSC2, ribosomal protein S10, TAP-144, gonadotropins, human gonadotropin releasing hormone 1, beta-lipotropin, octreotide, salmon calcitonin, des-n-octanoyl ghrelin, liraglutide, gastrins. Concepts were mapped to six physiological themes: altered endocrine function, 23.1%; inflammation or cytokine storm, 21.3%; lipid metabolism and atherosclerosis, 17.6%; sympathetic input to blood pressure regulation, 16.7%; altered entry of COVID-19 virus, 14.8%; and unknown, 6.5%.

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“…For collecting known ligands for this disease target, we search both literature and PDB database. We collect 38 known ligands for nsp13 through literature screening 35 – 38 , 53 , 54 . We also extract the ligands for nsp13 found in the PDB entries for nsp13 found in the relevant PDB entries.…”

Section: Methodsmentioning

confidence: 99%

Molecular-evaluated and explainable drug repurposing for COVID-19 using ensemble knowledge graph embedding

Islam

Amaya-Ramirez

Maigret

et al. 2023

Sci Rep

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The search for an effective drug is still urgent for COVID-19 as no drug with proven clinical efficacy is available. Finding the new purpose of an approved or investigational drug, known as drug repurposing, has become increasingly popular in recent years. We propose here a new drug repurposing approach for COVID-19, based on knowledge graph (KG) embeddings. Our approach learns “ensemble embeddings” of entities and relations in a COVID-19 centric KG, in order to get a better latent representation of the graph elements. Ensemble KG-embeddings are subsequently used in a deep neural network trained for discovering potential drugs for COVID-19. Compared to related works, we retrieve more in-trial drugs among our top-ranked predictions, thus giving greater confidence in our prediction for out-of-trial drugs. For the first time to our knowledge, molecular docking is then used to evaluate the predictions obtained from drug repurposing using KG embedding. We show that Fosinopril is a potential ligand for the SARS-CoV-2 nsp13 target. We also provide explanations of our predictions thanks to rules extracted from the KG and instanciated by KG-derived explanatory paths. Molecular evaluation and explanatory paths bring reliability to our results and constitute new complementary and reusable methods for assessing KG-based drug repurposing.

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The SARS-CoV-2 helicase as a target for antiviral therapy: Identification of potential small molecule inhibitors by in silico modelling

Cited by 9 publications

References 85 publications

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host

Computational exploration of the dual role of the phytochemical fortunellin: Antiviral activities against SARS-CoV-2 and immunomodulatory abilities against the host

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19

Molecular-evaluated and explainable drug repurposing for COVID-19 using ensemble knowledge graph embedding

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