tetano
Editor, Senior Moderator
Protein Sci
. 2023 Sep 1;e4773.
doi: 10.1002/pro.4773. Online ahead of print. Biophysical Investigation of Interactions Between SARS-CoV-2 Spike Protein and Neuropilin-1
Decheng Hou[SUP] 1 2 [/SUP], Wenpeng Cao[SUP] 1 [/SUP], Seonghan Kim[SUP] 1 [/SUP], Xinyu Cui[SUP] 1 2 [/SUP], Matthew Ziarnik[SUP] 1 [/SUP], Im Wonpil[SUP] 1 [/SUP], X Frank Zhang[SUP] 1 2 [/SUP]
Affiliations
Recent studies have suggested that neuropilin-1 (NRP1) may serve as a potential receptor in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, the biophysical characteristics of interactions between NRP1 and SARS-CoV-2 remain unclear. In this study, we examined the interactions between NRP1 and various SARS-CoV-2 spike (S) fragments, including the receptor-binding domain (RBD) and the S protein trimer in a soluble form or expressed on pseudovirions, using atomic force microscopy (AFM) and structural modeling. Our measurements showed that NRP1 interacts with the RBD and trimer at a higher binding frequency compared to ACE2. This NRP1-RBD interaction has also been predicted and simulated via AlphaFold2 and molecular dynamic simulations, and the results indicate that their binding patterns are very similar to RBD-ACE2 interactions. Additionally, under similar loading rates, the most probable unbinding forces between NRP1 and S trimer (both soluble form and on pseudovirions) are larger than the forces between NRP1 and RBD and between trimer and ACE2. Further analysis indicates that NRP1 has a stronger binding affinity to the SARS-CoV-2 S trimer with a dissociation rate of 0.87 s[SUP]-1[/SUP] , four times lower than the dissociation rate of 3.65 s[SUP]-1[/SUP] between NRP1 and RBD. Moreover, additional experiments show that RBD-neutralizing antibodies can significantly reduce the binding frequency for both ACE2 and NRP1. Together, the study suggests that NRP1 can be an alternative receptor for SARS-CoV-2 attachment to human cells, and the neutralizing antibodies targeting SARS-CoV-2 RBD can reduce the binding between SARS-CoV-2 and NRP1. This article is protected by copyright. All rights reserved.
Keywords: AlphaFold; MD simulation; SARS-CoV-2; force microscopy; neuropilin-1; virus-host cell interaction.
. 2023 Sep 1;e4773.
doi: 10.1002/pro.4773. Online ahead of print. Biophysical Investigation of Interactions Between SARS-CoV-2 Spike Protein and Neuropilin-1
Decheng Hou[SUP] 1 2 [/SUP], Wenpeng Cao[SUP] 1 [/SUP], Seonghan Kim[SUP] 1 [/SUP], Xinyu Cui[SUP] 1 2 [/SUP], Matthew Ziarnik[SUP] 1 [/SUP], Im Wonpil[SUP] 1 [/SUP], X Frank Zhang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 37656811
- DOI: 10.1002/pro.4773
Recent studies have suggested that neuropilin-1 (NRP1) may serve as a potential receptor in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, the biophysical characteristics of interactions between NRP1 and SARS-CoV-2 remain unclear. In this study, we examined the interactions between NRP1 and various SARS-CoV-2 spike (S) fragments, including the receptor-binding domain (RBD) and the S protein trimer in a soluble form or expressed on pseudovirions, using atomic force microscopy (AFM) and structural modeling. Our measurements showed that NRP1 interacts with the RBD and trimer at a higher binding frequency compared to ACE2. This NRP1-RBD interaction has also been predicted and simulated via AlphaFold2 and molecular dynamic simulations, and the results indicate that their binding patterns are very similar to RBD-ACE2 interactions. Additionally, under similar loading rates, the most probable unbinding forces between NRP1 and S trimer (both soluble form and on pseudovirions) are larger than the forces between NRP1 and RBD and between trimer and ACE2. Further analysis indicates that NRP1 has a stronger binding affinity to the SARS-CoV-2 S trimer with a dissociation rate of 0.87 s[SUP]-1[/SUP] , four times lower than the dissociation rate of 3.65 s[SUP]-1[/SUP] between NRP1 and RBD. Moreover, additional experiments show that RBD-neutralizing antibodies can significantly reduce the binding frequency for both ACE2 and NRP1. Together, the study suggests that NRP1 can be an alternative receptor for SARS-CoV-2 attachment to human cells, and the neutralizing antibodies targeting SARS-CoV-2 RBD can reduce the binding between SARS-CoV-2 and NRP1. This article is protected by copyright. All rights reserved.
Keywords: AlphaFold; MD simulation; SARS-CoV-2; force microscopy; neuropilin-1; virus-host cell interaction.