tetano
Editor, Senior Moderator
ACS Nano
. 2024 Oct 1.
doi: 10.1021/acsnano.4c04212. Online ahead of print. Unveiling the Dynamic Mechanism of SARS-CoV-2 Entry Host Cells at the Single-Particle Level
Siying Li[SUP] 1 [/SUP], Hui Yang[SUP] 2 3 [/SUP], Falin Tian[SUP] 4 [/SUP], Wei Li[SUP] 2 3 [/SUP], Hongda Wang[SUP] 5 [/SUP], Xinghua Shi[SUP] 3 4 [/SUP], Zongqiang Cui[SUP] 2 3 [/SUP], Yuping Shan[SUP] 1 [/SUP]
Affiliations
Understanding the dynamic features of severe acute respiratory coronavirus 2 (SARS-CoV-2) binding to the cell membrane and entry cells is crucial for comprehending viral pathogenesis and transmission and facilitating the development of effective drugs against COVID-19. Herein, we employed atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) to study the binding dynamics between the virus and cell membrane. Our findings revealed that the Omicron variant of SARS-CoV-2 virus-like particles (VLPs) exhibited a slightly stronger affinity for the angiotensin-converting enzyme-2 (ACE2) receptor compared with the Delta variant and was significantly higher than the wild-type (WT). Using a real-time force-tracing technique, we quantified the dynamic parameters for a single SARS-CoV-2 VLP entry into cells, showing that approximately 200 ms and 60 pN are required. The parameters aligned with the analysis obtained from coarse-grained molecular dynamics (CGMD) simulations. Additionally, the Omicron variant invades cells at a higher entry cell speed, smaller force, and higher probability. Furthermore, single-particle fluorescence tracking visually demonstrated clathrin-dependent endocytosis for SARS-CoV-2 entry into A549 cells. The dynamic features of endocytosis provide valuable insights into the SARS-CoV-2 entry mechanism and possible intervention strategies targeting the viral infection process.
Keywords: SARS-CoV-2; atomic force microscopy; entry cell dynamic mechanism; molecular dynamics simulations; single-particle fluorescence tracking.
. 2024 Oct 1.
doi: 10.1021/acsnano.4c04212. Online ahead of print. Unveiling the Dynamic Mechanism of SARS-CoV-2 Entry Host Cells at the Single-Particle Level
Siying Li[SUP] 1 [/SUP], Hui Yang[SUP] 2 3 [/SUP], Falin Tian[SUP] 4 [/SUP], Wei Li[SUP] 2 3 [/SUP], Hongda Wang[SUP] 5 [/SUP], Xinghua Shi[SUP] 3 4 [/SUP], Zongqiang Cui[SUP] 2 3 [/SUP], Yuping Shan[SUP] 1 [/SUP]
Affiliations
- PMID: 39353173
- DOI: 10.1021/acsnano.4c04212
Understanding the dynamic features of severe acute respiratory coronavirus 2 (SARS-CoV-2) binding to the cell membrane and entry cells is crucial for comprehending viral pathogenesis and transmission and facilitating the development of effective drugs against COVID-19. Herein, we employed atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) to study the binding dynamics between the virus and cell membrane. Our findings revealed that the Omicron variant of SARS-CoV-2 virus-like particles (VLPs) exhibited a slightly stronger affinity for the angiotensin-converting enzyme-2 (ACE2) receptor compared with the Delta variant and was significantly higher than the wild-type (WT). Using a real-time force-tracing technique, we quantified the dynamic parameters for a single SARS-CoV-2 VLP entry into cells, showing that approximately 200 ms and 60 pN are required. The parameters aligned with the analysis obtained from coarse-grained molecular dynamics (CGMD) simulations. Additionally, the Omicron variant invades cells at a higher entry cell speed, smaller force, and higher probability. Furthermore, single-particle fluorescence tracking visually demonstrated clathrin-dependent endocytosis for SARS-CoV-2 entry into A549 cells. The dynamic features of endocytosis provide valuable insights into the SARS-CoV-2 entry mechanism and possible intervention strategies targeting the viral infection process.
Keywords: SARS-CoV-2; atomic force microscopy; entry cell dynamic mechanism; molecular dynamics simulations; single-particle fluorescence tracking.