@misc{10481/79049,
year = {2022},
month = {12},
url = {https://hdl.handle.net/10481/79049},
abstract = {Since the beginning of the COVID-19 pandemic, considerable efforts have been made to
develop protective vaccines against SARS-CoV-2 infection. However, immunity tends to decline
within a few months, and new virus variants are emerging with increased transmissibility and
capacity to evade natural or vaccine-acquired immunity. Therefore, new robust strategies are needed
to combat SARS-CoV-2 infection. The viral spike composed of S1 and S2 subunits mediates viral
attachment and membrane fusion to infect the host cell. In this process, interaction between the highly
conserved heptad repeat 1 and 2 regions (HR1 and HR2) of S2 is crucial and for this reason; these
regions are promising targets to fight SARS-CoV-2. Here, we describe the design and characterization
of chimeric proteins that structurally imitate the S2 HR1 region in a trimeric coiled-coil conformation.
We biophysically characterized the proteins and determined their capacity to bind the HR2 region,
as well as their inhibitory activity of SARS-CoV-2 infection in vitro. HR1 mimetic proteins showed
conformational heterogeneity and a propensity to form oligomers. Moreover, their structure is
composed of subdomains with varied stability. Interestingly, the full HR1 proteins showed high
affinity for HR2-derived peptides and SARS-CoV-2 inhibitory activity, whereas smaller proteins
mimicking HR1 subdomains had a decreased affinity for their complementary HR2 region and did
not inhibit the virus. The results provide insight into effective strategies to create mimetic proteins
with broad inhibitory activity and therapeutic potential against SARS-CoV-2.},
organization = {Junta de Andalucia},
organization = {Spain's State Research Agency	CV20.26565	
ERDF/ESF	PID2019.107515RB.C21},
organization = {ANRS},
organization = {French National Research Agency (ANR)		
French National Research Agency (ANR)},
organization = {EHVA	ANR-10-LABX-77	
681032},
publisher = {MDPI},
keywords = {Coronavirus},
keywords = {Antivirals},
keywords = {Inhibitors},
keywords = {COVID-19},
keywords = {Calorimetry},
keywords = {Protein engineering},
keywords = {Protein design},
title = {Exploring Highly Conserved Regions of SARS-CoV-2 Spike S2 Subunit as Targets for Fusion Inhibition Using Chimeric Proteins},
doi = {10.3390/ijms232415511},
author = {Polo Megías, Daniel and Cano Muñoz, Mario and Berruezo, Alberto G. and Conejero Lara, Francisco},
}