التفاصيل البيبلوغرافية
| العنوان: |
Exploration of SARS-CoV‑2 3CL pro Inhibitors by Virtual Screening Methods, FRET Detection, and CPE Assay |
| المؤلفون: |
Jun Zhao (59250), Qinhai Ma (11731726), Baoyue Zhang (1397014), Pengfei Guo (421384), Zhe Wang (41178), Yi Liu (36759), Minsi Meng (11731729), Ailin Liu (758014), Zifeng Yang (3794932), Guanhua Du (620091) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Molecular Biology, Pharmacology, Infectious Diseases, Biological Sciences not elsewhere classified, Mathematical Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Information Systems not elsewhere classified, virtual screening methods, test set verification, maximal inhibitory concentration, fold cross verification, 369 chemical components, provide important information, maccs molecular fingerprints, certain antiviral effect, 5766 natural compounds, pro , machine learning algorithms, biological activity determination, antinovel coronavirus drugs, 50 , cpe assay covid, novel coronavirus, molecular descriptors, important part, cytopathic effect, cpe assay, anticoronavirus drugs |
| الوصف: |
COVID-19 caused by a novel coronavirus (SARS-CoV-2) has been spreading all over the world since the end of 2019, and no specific drug has been developed yet. 3C-like protease (3CL pro ) acts as an important part of the replication of novel coronavirus and is a promising target for the development of anticoronavirus drugs. In this paper, eight machine learning models were constructed using naïve Bayesian (NB) and recursive partitioning (RP) algorithms for 3CL pro on the basis of optimized two-dimensional (2D) molecular descriptors (MDs) combined with ECFP_4, ECFP_6, and MACCS molecular fingerprints. The optimal models were selected according to the results of 5-fold cross verification, test set verification, and external test set verification. A total of 5766 natural compounds from the internal natural product database were predicted, among which 369 chemical components were predicted to be active compounds by the optimal models and the EstPGood values were more than 0.6, as predicted by the NB (MD + ECFP_6) model. Through ADMET analysis, 31 compounds were selected for further biological activity determination by the fluorescence resonance energy transfer (FRET) method and cytopathic effect (CPE) detection. The results indicated that (+)-shikonin, shikonin, scutellarein, and 5,3′,4′-trihydroxyflavone showed certain activity in inhibiting SARS-CoV-2 3CL pro with the half-maximal inhibitory concentration (IC 50 ) values ranging from 4.38 to 87.76 μM. In the CPE assay, 5,3′,4′-trihydroxyflavone showed a certain antiviral effect with an IC 50 value of 8.22 μM. The binding mechanism of 5,3′,4′-trihydroxyflavone with SARS-CoV-2 3CL pro was further revealed through CDOCKER analysis. In this study, 3CL pro prediction models were constructed based on machine learning algorithms for the prediction of active compounds, and the activity of potential inhibitors was determined by the FRET method and CPE assay, which provide important information for further discovery and development of antinovel coronavirus drugs. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Exploration_of_SARS-CoV_2_3CL_sup_pro_sup_Inhibitors_by_Virtual_Screening_Methods_FRET_Detection_and_CPE_Assay/17052736 |
| DOI: |
10.1021/acs.jcim.1c01089.s002 |
| الاتاحة: |
https://doi.org/10.1021/acs.jcim.1c01089.s002 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.CC5F1B40 |
| قاعدة البيانات: |
BASE |