Objective To explore potential inhibitors of SARS-CoV-2 for the treatment of corona virus disease 2019(COVID-19)from Ruixiang Langdu(Sellera chamaejasme L.)and Langdu Daji(Euphorbia fischeriana Sud.)chemical compo-nents by In silico screening and in vitro Mpro inhibitory activity determination.Methods In silico screening of natural products from Ruixiang Langdu(Sellera chamaejasme L.)and Langdu Daji(Euphorbia fischeriana Sud.)were performed targeting on Mpro(PDB ID:6LU7).The original ligand N3 in 6LU7 was used as the control,the binding affinity and conformation were ana-lyzed.In vitro Mpro inhibitory activity determination was performed.Results Biflavonoids chamaejasmin and isochamaejasmin showed the highest binding affinities(-9.7 kcal/Mol)compared with N3(-7.7 kcal/Mol)and other known antiviral drugs in-cluding ritonavir,ganciclovir,ribavirin,chloroquine,darunavir,abacavir and other natural products.In binding conformation anal-ysis,isochamaejasmin showed more valuable hydrogen bond interactions with the key amino acid residues compared with chamae-jasmin,although both of them occupied the Mpro ligand-binding domain,which was important for the ligand-receptor binding as well as the stability of the binding confrmation.The isochamaejasmin showed better Mpro inhibitory activity than chamaejasmin at the concentration of 50 μM.Conclusion Chamaejasmin and isochamaejasmin might be potential inhibitors of SARS-CoV-2 Mpro,and could be served as leads for structure optimization as well as in vitro and in vivo anti-SARS-CoV-2 studies.
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