tetano
Editor, Senior Moderator
J Biol Chem
. 2022 Mar 9;101814.
doi: 10.1016/j.jbc.2022.101814. Online ahead of print.
Prefusion Spike Protein Conformational Changes Are Slower in SARS-CoV-2 than in SARS-CoV-1
Vivek Govind Kumar[SUP] 1 [/SUP], Dylan S Ogden[SUP] 1 [/SUP], Ugochi H Isu[SUP] 1 [/SUP], Adithya Polasa[SUP] 1 [/SUP], James Losey[SUP] 1 [/SUP], Mahmoud Moradi[SUP] 2 [/SUP]
Affiliations
Abstract
Within the last two decades, severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks; yet for reasons not fully understood, the COVID-19 pandemic caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1 despite striking similarities between these two viruses. The SARS-CoV-1 and SARS-CoV-2 spike proteins, both of which bind to host cell angiotensin converting enzyme 2 (ACE2), have been implied to be a potential source of their differential transmissibility. However, the mechanistic details of prefusion spike protein binding to ACE2 remain elusive at the molecular level. Here, we performed an extensive set of equilibrium and nonequilibrium microsecond-level all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and -2 prefusion spike proteins to determine their differential dynamic behavior. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. These results suggest that not only the receptor binding domain (RBD), but also other domains such as the N-terminal domain (NTD), could play a crucial role in the differential binding behavior of SARS-CoV-1 and -2 spike proteins.
. 2022 Mar 9;101814.
doi: 10.1016/j.jbc.2022.101814. Online ahead of print.
Prefusion Spike Protein Conformational Changes Are Slower in SARS-CoV-2 than in SARS-CoV-1
Vivek Govind Kumar[SUP] 1 [/SUP], Dylan S Ogden[SUP] 1 [/SUP], Ugochi H Isu[SUP] 1 [/SUP], Adithya Polasa[SUP] 1 [/SUP], James Losey[SUP] 1 [/SUP], Mahmoud Moradi[SUP] 2 [/SUP]
Affiliations
- PMID: 35278433
- DOI: 10.1016/j.jbc.2022.101814
Abstract
Within the last two decades, severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks; yet for reasons not fully understood, the COVID-19 pandemic caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1 despite striking similarities between these two viruses. The SARS-CoV-1 and SARS-CoV-2 spike proteins, both of which bind to host cell angiotensin converting enzyme 2 (ACE2), have been implied to be a potential source of their differential transmissibility. However, the mechanistic details of prefusion spike protein binding to ACE2 remain elusive at the molecular level. Here, we performed an extensive set of equilibrium and nonequilibrium microsecond-level all-atom molecular dynamics (MD) simulations of SARS-CoV-1 and -2 prefusion spike proteins to determine their differential dynamic behavior. Our results indicate that the active form of the SARS-CoV-2 spike protein is more stable than that of SARS-CoV-1 and the energy barrier associated with the activation is higher in SARS-CoV-2. These results suggest that not only the receptor binding domain (RBD), but also other domains such as the N-terminal domain (NTD), could play a crucial role in the differential binding behavior of SARS-CoV-1 and -2 spike proteins.