tetano
Editor, Senior Moderator
Pharmacol Res
. 2021 Aug 14;105820.
doi: 10.1016/j.phrs.2021.105820. Online ahead of print.
Identification of Natural Compounds as SARS-CoV-2 Entry Inhibitors by Molecular Docking-based Virtual Screening with Bio-layer Interferometry
Dingqi Zhang[SUP] 1 [/SUP], Sami Hamdoun[SUP] 2 [/SUP], Ruihong Chen[SUP] 2 [/SUP], Lijun Yang[SUP] 2 [/SUP], Chi Kio Ip[SUP] 3 [/SUP], Yuanqing Qu[SUP] 2 [/SUP], Runfeng Li[SUP] 2 [/SUP], Haiming Jiang[SUP] 4 [/SUP], Zifeng Yang[SUP] 5 [/SUP], Sookja Kim Chung[SUP] 6 [/SUP], Liang Liu[SUP] 7 [/SUP], Vincent Kam Wai Wong[SUP] 8 [/SUP]
Affiliations
Abstract
Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100μM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.
Keywords: SARS-CoV-2; bio-layer interferometry; competitive binding; molecular docking; molecular dynamics simulation; natural compounds.
. 2021 Aug 14;105820.
doi: 10.1016/j.phrs.2021.105820. Online ahead of print.
Identification of Natural Compounds as SARS-CoV-2 Entry Inhibitors by Molecular Docking-based Virtual Screening with Bio-layer Interferometry
Dingqi Zhang[SUP] 1 [/SUP], Sami Hamdoun[SUP] 2 [/SUP], Ruihong Chen[SUP] 2 [/SUP], Lijun Yang[SUP] 2 [/SUP], Chi Kio Ip[SUP] 3 [/SUP], Yuanqing Qu[SUP] 2 [/SUP], Runfeng Li[SUP] 2 [/SUP], Haiming Jiang[SUP] 4 [/SUP], Zifeng Yang[SUP] 5 [/SUP], Sookja Kim Chung[SUP] 6 [/SUP], Liang Liu[SUP] 7 [/SUP], Vincent Kam Wai Wong[SUP] 8 [/SUP]
Affiliations
- PMID: 34403732
- DOI: 10.1016/j.phrs.2021.105820
Abstract
Coronavirus Disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which enter the host cells through the interaction between its receptor binding domain (RBD) of spike glycoprotein with angiotensin-converting enzyme 2 (ACE2) receptor on the plasma membrane of host cell. Neutralizing antibodies and peptide binders of RBD can block viral infection, however, the concern of accessibility and affordability of viral infection inhibitors has been raised. Here, we report the identification of natural compounds as potential SARS-CoV-2 entry inhibitors using the molecular docking-based virtual screening coupled with bilayer interferometry (BLI). From a library of 1871 natural compounds, epigallocatechin gallate (EGCG), 20(R)-ginsenoside Rg3 (RRg3), 20(S)-ginsenoside Rg3 (SRg3), isobavachalcone (Ibvc), isochlorogenic A (IscA) and bakuchiol (Bkc) effectively inhibited pseudovirus entry at concentrations up to 100μM. Among these compounds, four compounds, EGCG, Ibvc, salvianolic acid A (SalA), and isoliensinine (Isl), were effective in inhibiting SARS-CoV-2-induced cytopathic effect and plaque formation in Vero E6 cells. The EGCG was further validated with no observable animal toxicity and certain antiviral effect against SARS-CoV-2 pseudovirus mutants (D614G, N501Y, N439K & Y453F). Interestingly, EGCG, Bkc and Ibvc bind to ACE2 receptor in BLI assay, suggesting a dual binding to RBD and ACE2. Current findings shed some insight into identifications and validations of SARS-CoV-2 entry inhibitors from natural compounds.
Keywords: SARS-CoV-2; bio-layer interferometry; competitive binding; molecular docking; molecular dynamics simulation; natural compounds.