Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12
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Abstract
The COVID-19 pandemic has accelerated the need to identify new therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir (RDV), the only antiviral against SARS-CoV-2 currently approved for human use, using a quantum-inspired device. We modelled RDV and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum Weighted Independent Set problem within the conflict graph generated. We also employed a traditional Tanimoto fingerprint model. The two methods yielded different lists of compounds, with some overlap. While GS-6620 was the top compound predicted by both models, the QUBO model predicted BMS-986094 as second best. The Tanimoto model predicted different forms of cobalamin, also known as vitamin B12. We then determined the half maximal inhibitory concentration (IC 50 ) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. Lastly, we demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Our data reveal that BMS-986094 and different forms of vitamin B12 are effective at inhibiting replication of all these variants of SARS-CoV-2. While BMS-986094 can cause secondary effects in humans as established by phase II trials, these findings suggest that vitamin B12 deserves consideration as a SARS-CoV-2 antiviral, particularly given its extended use and lack of toxicity in humans, and its availability and affordability. Our screening method can be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment.
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SciScore for 10.1101/2021.06.25.449609: (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
Experimental Models: Cell Lines Sentences Resources Cells: Vero E6 cells were kindly provided by W. Barclay (Imperial College London) and Caco-2 cells were kindly provided by C. Odendall (King’s College London). Caco-2suggested: CLS Cat# 300137/p1665_CaCo-2, RRID:CVCL_0025)Later, Vero E6 and Caco-2 cells were infected with SARS-CoV-2 England 02/2020/407073, B.1.1.7 or B.1.351 isolates at an MOIs of 0.05 and 0.5, respectively for 1 h. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources After getting the features described above, we generate the graphs with NetworkX49, a Python package for networks, in order to get an easier … SciScore for 10.1101/2021.06.25.449609: (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
Experimental Models: Cell Lines Sentences Resources Cells: Vero E6 cells were kindly provided by W. Barclay (Imperial College London) and Caco-2 cells were kindly provided by C. Odendall (King’s College London). Caco-2suggested: CLS Cat# 300137/p1665_CaCo-2, RRID:CVCL_0025)Later, Vero E6 and Caco-2 cells were infected with SARS-CoV-2 England 02/2020/407073, B.1.1.7 or B.1.351 isolates at an MOIs of 0.05 and 0.5, respectively for 1 h. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources After getting the features described above, we generate the graphs with NetworkX49, a Python package for networks, in order to get an easier representation of the molecules as well as for the conflict graph we needed to generate. Pythonsuggested: (IPython, RRID:SCR_001658)Later, Vero E6 and Caco-2 cells were infected with SARS-CoV-2 England 02/2020/407073, B.1.1.7 or B.1.351 isolates at an MOIs of 0.05 and 0.5, respectively for 1 h. SARS-CoV-2suggested: (BioLegend Cat# 944703, RRID:AB_2890874)Data were analysed using Prism 9.0 (GraphPad), and IC50 values were calculated by nonlinear regression analysis using the dose–response (variable slope) equation. Prismsuggested: (PRISM, RRID:SCR_005375)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT01629732 Withdrawn Phase 2b Study of BMS-986094 and Daclatasvir, With or Withou… 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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