tetano
Editor, Senior Moderator
Molecules
. 2020 Dec 24;26(1):E57.
doi: 10.3390/molecules26010057.
Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology
Zhi-Ling Zhu[SUP] 1 [/SUP], Xiao-Dan Qiu[SUP] 1 [/SUP], Shuo Wu[SUP] 1 [/SUP], Yi-Tong Liu[SUP] 1 [/SUP], Ting Zhao[SUP] 1 [/SUP], Zhong-Hao Sun[SUP] 1 [/SUP], Zhuo-Rong Li[SUP] 1 [/SUP], Guang-Zhi Shan[SUP] 1 [/SUP]
Affiliations
Abstract
The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (K[SUB]D[/SUB], μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.
Keywords: ACE2; COVID-19; SARS-CoV-2; protein–protein interaction inhibitors; receptor binding domain; surface plasmon resonance.
. 2020 Dec 24;26(1):E57.
doi: 10.3390/molecules26010057.
Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology
Zhi-Ling Zhu[SUP] 1 [/SUP], Xiao-Dan Qiu[SUP] 1 [/SUP], Shuo Wu[SUP] 1 [/SUP], Yi-Tong Liu[SUP] 1 [/SUP], Ting Zhao[SUP] 1 [/SUP], Zhong-Hao Sun[SUP] 1 [/SUP], Zhuo-Rong Li[SUP] 1 [/SUP], Guang-Zhi Shan[SUP] 1 [/SUP]
Affiliations
- PMID: 33374387
- DOI: 10.3390/molecules26010057
Abstract
The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019, and there is no sign that the epidemic is abating. Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. In this study, surface plasmon resonance (SPR) was used as the primary method to screen a library of 960 compounds. A compound 02B05 (demethylzeylasteral, CAS number: 107316-88-1) that had high affinities for S-RBD and ACE2 was discovered, and binding affinities (K[SUB]D[/SUB], μM) of 02B05-ACE2 and 02B05-S-RBD were 1.736 and 1.039 μM, respectively. The results of a competition experiment showed that 02B05 could effectively block the binding of S-RBD to ACE2 protein. Furthermore, pseudovirus infection assay revealed that 02B05 could inhibit entry of SARS-CoV-2 pseudovirus into 293T cells to a certain extent at nontoxic concentration. The compoundobtained in this study serve as references for the design of drugs which have potential in the treatment of COVID-19 and can thus accelerate the process of developing effective drugs to treat SARS-CoV-2 infections.
Keywords: ACE2; COVID-19; SARS-CoV-2; protein–protein interaction inhibitors; receptor binding domain; surface plasmon resonance.