Dirac semimetals are materials in which the conduction and the valence bands have robust crossing points protected by topology or symmetry. Recently, a new type of Dirac semimetals, so called the Dirac line-node semim...Dirac semimetals are materials in which the conduction and the valence bands have robust crossing points protected by topology or symmetry. Recently, a new type of Dirac semimetals, so called the Dirac line-node semimetals （DLNSs）, have attracted a lot of attention, as they host robust Dirac points along the one-dimensional （1D） lines in the Brillouin zone （BZ）. In this work, using angle-resolved photoemission spectroscopy （ARPES） and first-principles calculations, we systematically investigated the electronic structures of non-symmorphic ZrSiS crystal where we clearly distinguished the surface states from the bulk states. The photon-energy-dependent measurements further prove the existence of Dirac line node along the X-R direction. Remarkably, by in situ surface potassium doping, we clearly observed the different evolutions of the bulk and surface electronic states while proving the robustness of the Dirac line node. Our studies not only reveal the complete electronic structures of ZrSiS, but also demonstrate the method manipulating the electronic structure of the compound.展开更多
Hand,foot,and mouth disease(HFMD),primarily instigated by Coxsackievirus A16(CVA16),poses a serious health concern,necessitating effective therapeutic interventions.The RNA-dependent RNA polymerase(RdRp)of CVA16 emerg...Hand,foot,and mouth disease(HFMD),primarily instigated by Coxsackievirus A16(CVA16),poses a serious health concern,necessitating effective therapeutic interventions.The RNA-dependent RNA polymerase(RdRp)of CVA16 emerges as a promising drug target for HFMD treatment.This study presents an in-silico pipeline for the identification of potential RdRp inhibitors against CVA16.A library of 91 natural compounds derived from Bacopa monnieri(brahmi)was virtually screened against the CVA16 RdRp.Here,Bacobitacin D emerged as a promising hit molecule,forming 8 hydrogen bonds including key catalytic site residues(Asp^(238)and Asp^(329))within the RdRp active site.Further,molecular dynamics(MD)simulations and MM/GBSA binding free energy calculations was applied on the top three hits that were selected based on exhaustive docking scores(≤-9.55 kcal/mol).Bacobitacin D exhibited sustainable stability,as evidenced by minimal deviation(RMSD=0.75±0.02 nm)during a 100 ns MD simulation.Importantly,Bacopaside IV exhibited the lowestΔGTOTAL binding free energy(-23.70 kcal/mol),while Bacobitacin D displayed a comparableΔGTOTAL of19.14 kcal/mol.Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues,including Asp^(238)and Ser^(289).This comprehensive study confirmed Bacobitacin D as a potent inhibitor of CVA16 RdRp,offering a potential avenue for therapeutic intervention against HFMD.Experimental validation is required to confirm the inhibitory action of Bacobitacin D against HFMD.展开更多
基金Project supported by the National Key R&D Program of China(Grant No.2017YFA0305400)Chinese Academy of Science–Shanghai Science Research Center(Grant No.CAS-SSRC-YH-2015-01)+2 种基金the National Natural Science Foundation of China(Grant No.11674229)the Engineering and Physical Sciences Research Council Platform(Grant No.EP/M020517/1)the Hefei Science–Center Chinese Academy of Sciences(Grant No.2015HSC-UE013)
文摘Dirac semimetals are materials in which the conduction and the valence bands have robust crossing points protected by topology or symmetry. Recently, a new type of Dirac semimetals, so called the Dirac line-node semimetals （DLNSs）, have attracted a lot of attention, as they host robust Dirac points along the one-dimensional （1D） lines in the Brillouin zone （BZ）. In this work, using angle-resolved photoemission spectroscopy （ARPES） and first-principles calculations, we systematically investigated the electronic structures of non-symmorphic ZrSiS crystal where we clearly distinguished the surface states from the bulk states. The photon-energy-dependent measurements further prove the existence of Dirac line node along the X-R direction. Remarkably, by in situ surface potassium doping, we clearly observed the different evolutions of the bulk and surface electronic states while proving the robustness of the Dirac line node. Our studies not only reveal the complete electronic structures of ZrSiS, but also demonstrate the method manipulating the electronic structure of the compound.
文摘Hand,foot,and mouth disease(HFMD),primarily instigated by Coxsackievirus A16(CVA16),poses a serious health concern,necessitating effective therapeutic interventions.The RNA-dependent RNA polymerase(RdRp)of CVA16 emerges as a promising drug target for HFMD treatment.This study presents an in-silico pipeline for the identification of potential RdRp inhibitors against CVA16.A library of 91 natural compounds derived from Bacopa monnieri(brahmi)was virtually screened against the CVA16 RdRp.Here,Bacobitacin D emerged as a promising hit molecule,forming 8 hydrogen bonds including key catalytic site residues(Asp^(238)and Asp^(329))within the RdRp active site.Further,molecular dynamics(MD)simulations and MM/GBSA binding free energy calculations was applied on the top three hits that were selected based on exhaustive docking scores(≤-9.55 kcal/mol).Bacobitacin D exhibited sustainable stability,as evidenced by minimal deviation(RMSD=0.75±0.02 nm)during a 100 ns MD simulation.Importantly,Bacopaside IV exhibited the lowestΔGTOTAL binding free energy(-23.70 kcal/mol),while Bacobitacin D displayed a comparableΔGTOTAL of19.14 kcal/mol.Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues,including Asp^(238)and Ser^(289).This comprehensive study confirmed Bacobitacin D as a potent inhibitor of CVA16 RdRp,offering a potential avenue for therapeutic intervention against HFMD.Experimental validation is required to confirm the inhibitory action of Bacobitacin D against HFMD.
