Small-molecule inhibitors that block the binding of covid-19 spike protein to human angiotensin-converting enzyme 2 and uses thereof
A COVID-19, small molecule inhibitor technology, applied in the fields of peptide/protein components, active ingredients of hydroxyl compounds, medical preparations containing active ingredients, etc. question
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Embodiment 1
[0039] Example 1: Primary screening of compounds
[0040] Virtual screening is conducted with the laboratory's own 145 molecular databases and 1913 marketed small molecule drugs as screening objects. The virtual screening software used in this embodiment is Discovery Studio. According to the virtual screening score, the list of potential molecules is selected according to the molecular structure characteristics. In this example, the compounds shown in Table 1 below were selected, wherein, the disulfonated derivative of luteolin, MXCS-diSO 3 Na (DUT202001, DUT202002) were synthesized by the following example 2, resveratrol analog (DUT202003), quercetin disulfonated derivative (DUT202004) were laboratory-owned, cerulein DUT202005, acarbose DUT202006 , Aliskiren (DUT202007) and the luteolin used in the examples were purchased commercially.
[0041] Table 1 Compound Information
[0042]
[0043]
Embodiment 2
[0044] Example 2: DUT202001 [2-(4,5-dihydroxyphenyl)-5,7-dihydroxy-benzo-γ-pyrone-3′,6-disulfonate sodium (also known as: luteolin) (Sodium-3',6-disulfonate)] and DUT202002[2-(4,5-dihydroxyphenyl)-5,7-dihydroxy-benzo-γ-pyrone-3',8- Synthesis of sodium disulfonate (also known as: luteolin-3', 8-sodium disulfonate)]
[0045] Measure 4mL of concentrated sulfuric acid in a 50mL chicken heart bottle, cool it to 0°C in an ice-water bath, add 1.0g luteolin powder in batches under stirring, heat up after the addition, react at 30°C for 72h, transfer the reaction solution into 50mL The saturated aqueous sodium chloride solution was stirred, and a large amount of solid was precipitated, and it was left to stand until the solid was completely precipitated, and then suction filtration under reduced pressure. The product was dissolved in 40 mL of deionized water, the pH value was adjusted to 6-7 with sodium bicarbonate, 2.0 g of sodium chloride was added for salting out, the precipitated ...
Embodiment 3
[0048] Example 3: Activity test for blocking the binding of the receptor binding domain (RBD) of the COVID-19 spike protein to human angiotensin-converting enzyme 2 (hACE2)
[0049] Experimental materials: compounds DUT202001 and DUT202002 (synthesized in Example 2), DUT202003 and DUT202004 (laboratory); compounds DUT202005, DUT202006 and DUT202007 (purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.); SARS-CoV-2S, pAX2, pHB, and ACE2-pcDNA3 (China Science and Technology Co., Ltd.); 293T cells (Shanghai Heyuan Biotechnology Co., Ltd.). The pCMV-SNAP-hACE2 plasmid, SNAP-561 fluorescent dye and RBD541-Halo-640dye were from the research group of Xu Zhaochao, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
[0050] Specifically, the test steps are as follows:
[0051]1) Select the luteolin disulfonated derivative MXCS-diSO with a virtual screening normalized FitValue score of 0.3966 in Example 1 3 Na(DUT202001), MXCS-diSO of luteolin disulfonated ...
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