In silico screening and testing of FDA approved small molecules to block SARS-CoV-2 entry to the host cell by inhibiting Spike protein cleavage
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Abstract
The COVID-19 pandemic began in 2019, but it is still active. The development of an effective vaccine reduced the number of deaths; however, a treatment is still needed. Here, we aimed to inhibit viral entry to the host cell by inhibiting Spike (S) protein cleavage by several proteases. We develop a computational pipeline to repurpose FDA-approved drugs to inhibit protease activity and thus prevent S protein cleavage. We tested some of our drug candidates and demonstrated a decrease in protease activity. We believe our pipeline will be beneficial in identifying a drug regimen for COVID-19 patients.
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SciScore for 10.1101/2022.03.07.483324: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources In order to obtain, mutant S2’ monomer and mutant S2’-trypsin complexes, PyMol (version 2.3.2) built-in Mutagenesis tool was used. PyMolsuggested: (PyMOL, RRID:SCR_000305)4.1.4 Small molecule libraries and structure based in silico screening: Clinically approved small molecules from the following drug libraries were used for screening; ZINC library of ∼1,650 molecules (33), DrugBank of ∼ 2,500 molecules (34), The Binding Database of ∼1,340 molecules (35) and ChemBridge of ∼50 molecules (top 50 hits from Elshabrawy et al (15)) obtained from Chembridge Corporation (San Diego,CA). ZINCsuggested…SciScore for 10.1101/2022.03.07.483324: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources In order to obtain, mutant S2’ monomer and mutant S2’-trypsin complexes, PyMol (version 2.3.2) built-in Mutagenesis tool was used. PyMolsuggested: (PyMOL, RRID:SCR_000305)4.1.4 Small molecule libraries and structure based in silico screening: Clinically approved small molecules from the following drug libraries were used for screening; ZINC library of ∼1,650 molecules (33), DrugBank of ∼ 2,500 molecules (34), The Binding Database of ∼1,340 molecules (35) and ChemBridge of ∼50 molecules (top 50 hits from Elshabrawy et al (15)) obtained from Chembridge Corporation (San Diego,CA). ZINCsuggested: (Zinc, RRID:SCR_008596)DrugBanksuggested: (DrugBank, RRID:SCR_002700)The mechanism of action data was curated from PubChem database (38). PubChemsuggested: (PubChem, RRID:SCR_004284)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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