论文出处：
https://www.biorxiv.org/content/10.1101/2021.06.25.449609v1.full
Drug repurposing based on a Quantum-Inspired method versus classical
fingerprinting uncovers potential antivirals against SARS-CoV-2 including
vitamin B12
Remdesivir (RDV) 是目前唯一获准用于人类使用的抗 SARS-CoV-2 抗病毒药物。
通过模型演算后，发现 GS-6620 是两种模型预测的最佳化合物，但 QUBO 模型预测
BMS-986094 位居第二。Tanimoto 模型预测了不同形式的钴胺素，也称为维生素 B12。
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.
维基百科已有GS-6620和维生素 B12页面
GS-6620是一种核苷酸类的抗病毒药物，被开发用于治疗C型肝炎。尽管它在早期测试中显
示出有效的抗病毒作用，但由于它在肠道中的吸收率低且效果不稳定（无法预测血液中的
浓度），未能成功制成口服剂。目前进行的研究主要针对其它疾病（如伊波拉出血热）的
治疗。
维生素B12一词有两种不同含义。一是广义上指一组含钴化合物即钴胺素（cobalamins）
：氰钴胺（cyanocobalamin，经氰化物提纯而成的人工成品）、羟钴胺（
hydroxocobalamin，即维生素B12α）及维生素B12的两种辅酶形式，甲钴胺（
methylcobalamin, MeB12）和5-去氧腺苷钴胺素（5-deoxyadenosylcobalamin），又名腺
苷钴胺（adenosylcobalamin, AdoB12）。二是更特定的含义，仅指以上各种形式中的一
种即氰钴胺，是B12来自食物和营养补充的主要形式。
BMS-986094药物识别公开页面
https://www.wikidata.org/wiki/Q27263478