Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo

Collins, Douglas A.

doi:10.1007/s11307-018-1232-9

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…Upon cyanide poisoning, adults can receive up to 5g of hydroxocobalamin as an antidote intravenously, which would be well within the range of our calculated IC 50 of 403µM. Moreover, previous studies on imaging show biodistribution of an intravenous In-111 labeled 5-deoxyadenosylcobalamin (AC) analog ([111In]AC) in nasal cavity and salivary glands 45 . There is also previous evidence of vitamin B12 having potential antiviral effects.…”

Section: Discussionsupporting

confidence: 78%

Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12

Jiménez-Guardeño

Ortega-Prieto

Bm³

et al. 2021

Preprint

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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 (IC50) 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.

show abstract

Section: Discussionsupporting

confidence: 78%

Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12

Jiménez-Guardeño

Ortega-Prieto

Bm³

et al. 2021

Preprint

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show abstract

“…When treating individuals with cyanide poisoning, adults generally receive 5g of hydroxocobalamin as an antidote intravenously (~70mg/kg) [ 44 ], which would be close to the range of our calculated IC 50 of 403μM (100 mg/kg). Previous imaging studies show biodistribution of an intravenous indium-111 labeled 5-deoxyadenosylcobalamin (AC) analog ([111In]AC) in the nasal cavity and salivary glands [ 45 ], key anatomical sites for SARS-CoV-2 replication. Intriguingly, there is also evidence for vitamin B12 having potential antiviral effects, with vitamin B12 supplementation improving outcome in hepatitis C virus (HCV) infection [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Drug repurposing based on a quantum-inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2

Jiménez-Guardeño

Ortega-Prieto

Moreno³

et al. 2022

PLoS Comput Biol

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The COVID-19 pandemic has accelerated the need to identify new antiviral therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir, the first antiviral against SARS-CoV-2 approved for human use, using a quantum-inspired device. We modelled Remdesivir 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 lead 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 (IC50) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. We also 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). Lastly, we employed an in vitro polymerization assay to demonstrate that these compounds directly inhibit the RNA-dependent RNA polymerase (RdRP) of SARS-CoV-2. Together, our data reveal that our QUBO model performs accurate comparisons (BMS-986094) that differed from those predicted by Tanimoto (different forms of vitamin B12); all compounds inhibited replication of SARS-CoV-2 via direct action on RdRP, with both models being useful. While Tanimoto may be employed when performing relatively small comparisons, QUBO is also accurate and may be well suited for very complex problems where computational resources may limit the number and/or complexity of possible combinations to evaluate. Our quantum-inspired screening method can therefore be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment.

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Production of cobalt-57 for industrial and medical applications in RFT-30 cyclotron facility

Lee

Chae

Lee

et al. 2023

J Radioanal Nucl Chem

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Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo

Cited by 5 publications

References 48 publications

Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12

Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12

Drug repurposing based on a quantum-inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2

Production of cobalt-57 for industrial and medical applications in RFT-30 cyclotron facility

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