[爆卦] 兩種C肝藥物與B12被認為可以控制疫情已回收

看板Gossiping作者GETpoint (擲雷爆卦)時間4年前 (2021/06/29 21:25)推噓16(16推 0噓 12→)

留言28則, 23人參與討論串1/2 (看更多)

論文出處： 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) 是目前唯一獲準用於人類使用的抗 SARS-CoV-2 抗病毒藥物。通過模型演算後，發現 GS-6620 是兩種模型預測的最佳化合物，但 QUBO 模型預測 BMS-986094 位居第二。Tanimoto 模型預測了不同形式的鈷胺素，也稱為維生素 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. 維基百科已有GS-6620和維生素 B12頁面 GS-6620是一種核苷酸類的抗病毒藥物，被開發用於治療C型肝炎。儘管它在早期測試中顯示出有效的抗病毒作用，但由於它在腸道中的吸收率低且效果不穩定（無法預測血液中的濃度），未能成功製成口服劑。目前進行的研究主要針對其它疾病（如伊波拉出血熱）的治療。維生素B12一詞有兩種不同含義。一是廣義上指一組含鈷化合物即鈷胺素（cobalamins）：氰鈷胺（cyanocobalamin，經氰化物提純而成的人工成品）、羥鈷胺（ hydroxocobalamin，即維生素B12α）及維生素B12的兩種輔酶形式，甲鈷胺（ methylcobalamin, MeB12）和5-去氧腺苷鈷胺素（5-deoxyadenosylcobalamin），又名腺苷鈷胺（adenosylcobalamin, AdoB12）。二是更特定的含義，僅指以上各種形式中的一種即氰鈷胺，是B12來自食物和營養補充的主要形式。 BMS-986094藥物識別公開頁面 https://www.wikidata.org/wiki/Q27263478 -- 七魄興輪無上伊甸瑜珈雖然是以看來較為平和的方式以蟬蛻和生乳取代血肉等腥穢之物作為密義源起供養；然而聚歛於上的是冥界的深冤與大樂奔瀉的淨慈，行者於閉關修持之時若生起退失動搖之心，則神識旋即離散且肉身消殞；即便如此還是願意受灌頂嗎？ https://imgur.com/cEVD0kE