Blocking Effect of Demethylzeylasteral on the Interaction between Human ACE2 Protein and SARS-CoV-2 RBD Protein Discovered Using SPR Technology |
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| Authors: | Zhi-Ling Zhu Xiao-Dan Qiu Shuo Wu Yi-Tong Liu Ting Zhao Zhong-Hao Sun Zhuo-Rong Li Guang-Zhi Shan |
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| Affiliation: | Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; (Z.-L.Z.); (X.-D.Q.); (S.W.); (Y.-T.L.); (T.Z.); (Z.-H.S.) |
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| 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 (KD, 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. |
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| Keywords: | SARS-CoV-2, COVID-19, surface plasmon resonance, protein– protein interaction inhibitors, ACE2, receptor binding domain |
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