tetano
Editor, Senior Moderator
Acta Pharmacol Sin
. 2021 Aug 4.
doi: 10.1038/s41401-021-00735-z. Online ahead of print.
Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein
Lin Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yan Wu[SUP] #[/SUP][SUP] 3 [/SUP], Sheng Yao[SUP] #[/SUP][SUP] 4 5 [/SUP], Huan Ge[SUP] #[/SUP][SUP] 6 [/SUP], Ya Zhu[SUP] 7 [/SUP], Kun Chen[SUP] 7 [/SUP], Wen-Zhang Chen[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Wei Zhu[SUP] 1 [/SUP], Hong-Yang Wang[SUP] 2 [/SUP], Yu Guo[SUP] 8 [/SUP], Pei-Xiang Ma[SUP] 1 [/SUP], Peng-Xuan Ren[SUP] 1 2 [/SUP], Xiang-Lei Zhang[SUP] 1 2 [/SUP], Hui-Qiong Li[SUP] 1 2 [/SUP], Mohammad A Ali[SUP] 9 [/SUP], Wen-Qing Xu[SUP] 2 [/SUP], Hua-Liang Jiang[SUP] 1 7 [/SUP], Lei-Ke Zhang[SUP] 10 [/SUP], Li-Li Zhu[SUP] 11 12 [/SUP], Yang Ye[SUP] 13 14 [/SUP], Wei-Juan Shang[SUP] 15 [/SUP], Fang Bai[SUP] 16 17 [/SUP]
Affiliations
Abstract
An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant K[SUB]D[/SUB]) of 0.0947 µM and anti-virus IC[SUB]50[/SUB] of 85.75 µM.
Keywords: SARS-CoV-2; natural products; protein-protein interaction modulators; spike protein; virtual screening.
. 2021 Aug 4.
doi: 10.1038/s41401-021-00735-z. Online ahead of print.
Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein
Lin Wang[SUP] #[/SUP][SUP] 1 2 [/SUP], Yan Wu[SUP] #[/SUP][SUP] 3 [/SUP], Sheng Yao[SUP] #[/SUP][SUP] 4 5 [/SUP], Huan Ge[SUP] #[/SUP][SUP] 6 [/SUP], Ya Zhu[SUP] 7 [/SUP], Kun Chen[SUP] 7 [/SUP], Wen-Zhang Chen[SUP] 1 [/SUP], Yi Zhang[SUP] 1 [/SUP], Wei Zhu[SUP] 1 [/SUP], Hong-Yang Wang[SUP] 2 [/SUP], Yu Guo[SUP] 8 [/SUP], Pei-Xiang Ma[SUP] 1 [/SUP], Peng-Xuan Ren[SUP] 1 2 [/SUP], Xiang-Lei Zhang[SUP] 1 2 [/SUP], Hui-Qiong Li[SUP] 1 2 [/SUP], Mohammad A Ali[SUP] 9 [/SUP], Wen-Qing Xu[SUP] 2 [/SUP], Hua-Liang Jiang[SUP] 1 7 [/SUP], Lei-Ke Zhang[SUP] 10 [/SUP], Li-Li Zhu[SUP] 11 12 [/SUP], Yang Ye[SUP] 13 14 [/SUP], Wei-Juan Shang[SUP] 15 [/SUP], Fang Bai[SUP] 16 17 [/SUP]
Affiliations
- PMID: 34349236
- DOI: 10.1038/s41401-021-00735-z
Abstract
An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant K[SUB]D[/SUB]) of 0.0947 µM and anti-virus IC[SUB]50[/SUB] of 85.75 µM.
Keywords: SARS-CoV-2; natural products; protein-protein interaction modulators; spike protein; virtual screening.