The ability of SARS-CoV-2 to replicate in host cells is dependent on its main protease (M, 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 of SARS-CoV-2 and inhibits its activity. Protein fluorescence quenching showed that heparin strongly binds to the M protein with dissociation constants K 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 with an inhibition constant Ki of 6.9 nM and a half maximal inhibitory concentrations (IC) 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 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 activity of SARS-CoV-2.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591854 | PMC |
http://dx.doi.org/10.1016/j.saa.2021.120595 | DOI Listing |
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