Furin cleavage of the SARS-CoV-2 spike protein results in a polybasic terminal sequence termed the C-end rule (CendR), which is responsible for the binding to neuropilin 1 (NRP1), enhancing viral infectivity and entry into the cell. Here we report the identification of 20 small-molecule inhibitors that emerged from a virtual screening of nearly 950,000 drug-like compounds that bind with high probability to the CendR-binding pocket of NRP1. In a spike NRP1 binding assay, two of these compounds displayed a stronger inhibition of spike protein binding to NRP1 than the known NRP1 antagonist EG00229 , for which the inhibition of the CendR peptide binding to NRP1 was also experimentally confirmed. These compounds present a good starting point for the design of small-molecule antagonists against the SARS-CoV-2 viral entry.
【저자키워드】 COVID-19, SARS-CoV-2, molecular docking, Virtual screening, neuropilin 1, spike binding inhibitors, small-molecule antagonists, in vitro binding assay, 【초록키워드】 peptide, viral entry, Spike protein, Probability, viral infectivity, NRP1, furin cleavage, inhibitor, binding, starting point, Compound, sequence, antagonist, Cell, responsible, these compound, polybasic, the SARS-CoV-2, 【제목키워드】 spike, novel, the SARS-CoV-2,