Virtual Screening of Chinese Medicine Small Molecule Compounds Targeting SARS-CoV-2 3CL protease (3CL pro)

2020 ◽  
Vol 17 ◽  
Author(s):  
Qingxiu He ◽  
Xin Chen ◽  
Xi Yang ◽  
Guangpin Li ◽  
Haiqiong Guo ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Virtual Screening ◽  
Natural Product ◽  
Binding Affinity ◽  
Binding Mode ◽  
Good Potential ◽  
Binding Energy Analysis ◽  
Analysis Platform ◽  
3Cl Protease ◽  
High Binding Affinity

: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted worldwide attention due to its high infectivity and pathogenicity. Objective: The purpose of this study is to develop drugs with therapeutic potentials for COVID-19. Methods: We selected the crystal structure of 3CL pro to perform virtual screening against natural products in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then, molecular dynamics (MD) simulation was carried out to explore the binding mode between compounds and 3CL pro. Results and Discussion: A total of 6 candidates with good theoretical binding affinity to 3CL pro were identified. The binding mode after MD shows that hydrogen bonding and hydrophobic interaction play an important role in the binding process. Finally, based on the free binding energy analysis, the candidate natural product Gypenoside LXXV may bind to 3CL pro with high binding affinity. Conclusion: The natural product Gypenoside LXXV may have good potential anti-SARS-COV-2 activity.

scholarly journals A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry

2021 ◽  
Vol 118 (50) ◽  
pp. e2112942118
Author(s):  
Julián Valero ◽  
Laia Civit ◽  
Daniel M. Dupont ◽  
Denis Selnihhin ◽  
Line S. Reinert ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Single Molecule ◽  
Viral Entry ◽  
New Technologies ◽  
Binding Mode ◽  
Dispersion Analysis ◽  
Rna Aptamer ◽  
Receptor Binding Domain ◽  
High Binding Affinity

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an urgent need for new technologies to treat COVID-19. Here we report a 2′-fluoro protected RNA aptamer that binds with high affinity to the receptor binding domain (RBD) of SARS-CoV-2 spike protein, thereby preventing its interaction with the host receptor ACE2. A trimerized version of the RNA aptamer matching the three RBDs in each spike complex enhances binding affinity down to the low picomolar range. Binding mode and specificity for the aptamer–spike interaction is supported by biolayer interferometry, single-molecule fluorescence microscopy, and flow-induced dispersion analysis in vitro. Cell culture experiments using virus-like particles and live SARS-CoV-2 show that the aptamer and, to a larger extent, the trimeric aptamer can efficiently block viral infection at low concentration. Finally, the aptamer maintains its high binding affinity to spike from other circulating SARS-CoV-2 strains, suggesting that it could find widespread use for the detection and treatment of SARS-CoV-2 and emerging variants.

scholarly journals Nano-evolution and protein-based enzymatic evolution predicts the novel types of natural product nanozyme of traditional Chinese medicine: cases of herbzymes of Taishan-Huangjing (Rhizoma polygonati) and Goji (Lycium chinense)

2021 ◽  
Author(s):  
Guldan Nazarbek ◽  
Aidana Kutzhanova ◽  
Lazzat Nurtay ◽  
Chenglin Mu ◽  
Bexultan Kazybay ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Natural Product ◽  
Enzyme Function ◽  
The Novel ◽  
Lycium Chinense ◽  
Natural Protein

Nanozyme and natural product-derived herbzyme have been identified in different enzyme types simulating the natural protein-based enzyme function. How to explore and predict enzyme types of novel nanozyme when synthesized...

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

scholarly journals The Detection of Bovine Estrus by Lactoferrin Monoclonal Antibody

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1582
Author(s):  
Jihwan Lee ◽  
Suhyun Lee ◽  
Younbae Park ◽  
Seokhyun Lee ◽  
Seungmin Ha ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Binding Affinity ◽  
Reproductive Performance ◽  
Economic Loss ◽  
Cervical Mucus ◽  
Female Rats ◽  
Economic Damage ◽  
Bovine Lactoferrin ◽  
Estrous Synchronization ◽  
High Binding Affinity

To improve reproductive performance in cattle, the accurate detection of estrus and optimization of insemination relative to ovulation are necessary. However, poor heat detection by farm staff leads to a decreased conception rate, thus inflicting economic damage to the beef and dairy industries. This study aimed to develop monoclonal antibodies (mAb) that can specifically bind to the bovine lactoferrin (bLF) protein, which we have previously demonstrated to be overexpressed in bovine cervical mucus during estrus. Female rats were intraperitoneally immunized with bLF protein as the antigen. Anti-bLF mAbs were then purified by affinity chromatography, and their binding affinity for the bLF antigen was examined using ELISA. We found a high binding affinity between mAbs and bLF. Finally, we developed a rapid bovine heat detection kit using the anti-bLF mAbs that we generated and tested on cervical mucus from 12 cows (estrous synchronization, n = 2; natural cycling, n = 10). We found that the kits accurately detected estrus. Overall, our fabricated heat detection kit based on rat anti-bLF mAbs could pave the way for the development of potent tools for heat detection devices for dairy cattle, thereby preventing economic loss.

scholarly journals Nucleic binding affinity of bacteriophage T4 gene 32 protein in the cooperative binding mode.

1982 ◽  
Vol 257 (11) ◽  
pp. 6184-6193
Author(s):  
A M Bobst ◽  
P W Langemeier ◽  
P E Warwick-Koochaki ◽  
E V Bobst ◽  
J C Ireland
Keyword(s):  
Binding Affinity ◽  
Bacteriophage T4 ◽  
Binding Mode ◽  
Cooperative Binding ◽  
Gene 32 ◽  
T4 Gene 32 Protein

scholarly journals Structural basis of subunit selectivity for competitive NMDA receptor antagonists with preference for GluN2A over GluN2B subunits

2017 ◽  
Vol 114 (33) ◽  
pp. E6942-E6951 ◽  
Author(s):  
Genevieve E. Lind ◽  
Tung-Chung Mou ◽  
Lucia Tamborini ◽  
Martin G. Pomper ◽  
Carlo De Micheli ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Binding Affinity ◽  
Binding Mode ◽  
Structural Basis ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Glutamate Binding ◽  
Subunit Interface ◽  
The Central Nervous System ◽  
Contact Residues

NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A–D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B. Crystal structures of the GluN1/2A agonist binding domain (ABD) heterodimer with bound ACEPC antagonists reveal a binding mode in which the ligands occupy a cavity that extends toward the subunit interface between GluN1 and GluN2A ABDs. Mutational analyses show that the GluN2A preference of ST3 is primarily mediated by four nonconserved residues that are not directly contacting the ligand, but positioned within 12 Å of the glutamate binding site. Two of these residues influence the cavity occupied by ST3 in a manner that results in favorable binding to GluN2A, but occludes binding to GluN2B. Thus, we reveal opportunities for the design of subunit-selective competitive NMDA receptor antagonists by identifying a cavity for ligand binding in which variations exist between GluN2A and GluN2B subunits. This structural insight suggests that subunit selectivity of glutamate-site antagonists can be mediated by mechanisms in addition to direct contributions of contact residues to binding affinity.

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