Abstract
The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (M pro , also called 3CLpro) that cut the viral precursor polyproteins and is a major target for antiviral drug design. Here, we showed that heparin interacts with the M pro of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the M pro protein with dissociation constants K D of 16.66 and 31.60 μM at 25 and 35 °C, respectively. From thermodynamic parameters of the interaction, there are hydrophobic and hydrogen bond interactions between them. Fluorescence resonance energy transfer (FRET) assay demonstrated that heparin inhibits the proteolytic activity of M pro with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC 50 ) of 7.8 ± 2.6 nM. Furthermore, molecular docking analysis revealed that the recognition and binding groups of heparin within the active site of SARS-CoV-2 M pro provide important new information for the characteristics of the interactions of heparin with the protease. Our finding suggested that heparin might have a potential role in inhibiting SARS-CoV-2 infection through inhibiting M pro activity of SARS-CoV-2.
Keywords: Activity; Heparin; Inhibitory effects; Interaction; Main protease; SARS-CoV-2.
【저자키워드】 main protease, heparin, SARS-CoV-2., activity, Inhibitory effects, Interaction, 【초록키워드】 SARS-CoV-2, SARS-COV-2 infection, 3CLpro, protease, heparin, antiviral drug, Protein, Characteristics, Fluorescence, group, information, binding, Inhibitory effects, host cells, host cell, active site, hydrogen, energy transfer, Recognition, M pro, hydrophobic, inhibitory concentration, proteolytic activity, molecular docking analysis, precursor, parameter, polyprotein, Fluorescence quenching, bind, inhibit, replicate, dependent on, demonstrated, suggested, interact, inhibiting, thermodynamic, hydrogen bond interaction, 【제목키워드】 SARS-CoV-2, inhibit, interact,