High-Potency Polypeptide-based Interference for Coronavirus Spike Glycoproteins [post]

Qinghua Wang, Jianpeng Ma, Adam Acevedo
2021 unpublished
The world is experiencing an unprecedented coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 spike protein-based vaccines are currently the main preventive agent to fight against the virus. However, several variants with extensive mutations in SARS-CoV-2 spike proteins have emerged. Some of these variants exhibited increased replication, higher transmission and virulence, and were partially resistant to antibody
more » ... t to antibody neutralization from natural infection or vaccination. With over 130 million confirmed cases and widespread vaccination around the globe, the emergence of new escape SARS-CoV-2 variants could be accelerated. New therapeutics insensitive to mutations are thus urgently needed. Here we have developed an inhibitor based on SARS-CoV-2 spike protein that potently reduced pseudovirus infectivity by limiting the level of SARS-CoV-2 spike proteins on virion envelope. Most importantly, the inhibitor was equally effective against other coronavirus spike proteins that shared as low as 35% amino-acid sequence identity, underscoring its extreme tolerance to mutations. The small-sized inhibitor would also allow simple delivery by, for instance, nasal spray. We expect the inhibitor reported here to be an invaluable aid to help end COVID-19 pandemic. Furthermore, the use of a partial native sequence or its homologues to interfere with the functions of the native protein represents a novel concept for targeting other viral proteins in combating against important viral pathogens.
doi:10.21203/rs.3.rs-388285/v1 fatcat:psp3wgkhmfgezeqleahdka7ru4