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Neuropilin-1 is a host factor for SARS-CoV-2 infection.
James L Daly1, Boris Simonetti2, Katja Klein3
1School of Biochemistry, Faculty of Life Sciences, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
Science (New York, N.Y.)
|October 21, 2020
Summary
The SARS-CoV-2 spike protein binds to host cell receptors via a CendR motif. This interaction with neuropilin-1 (NRP1) is crucial for virus entry, suggesting NRP1 as a potential therapeutic target for COVID-19.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19.
- The viral spike (S) protein mediates host cell attachment and entry.
- Host protease furin cleaves the S protein into S1 and S2 subunits.
Purpose of the Study:
- To investigate the interaction between the SARS-CoV-2 S1 subunit and host cell receptors.
- To determine the role of neuropilin-1 (NRP1) and NRP2 in SARS-CoV-2 infection.
Main Methods:
- X-ray crystallography to visualize the S1 CendR motif binding to NRP1.
- Biochemical assays to confirm the interaction.
- RNA interference and selective inhibitors to block the interaction.
- Cell culture experiments to assess viral entry and infectivity.
Main Results:
- The S1 CendR motif directly binds to the NRP1 receptor.
- Blocking the S1-NRP1 interaction reduced SARS-CoV-2 entry and infectivity in cell culture.
- NRP1 acts as a host factor facilitating SARS-CoV-2 infection.
Conclusions:
- Neuropilin-1 (NRP1) is a critical host factor for SARS-CoV-2 infection.
- Targeting the S1-NRP1 interaction may offer a therapeutic strategy against COVID-19.
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