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Upon infection HR1 undergoes a “jackknife” transition that can insert the fusion peptide (FP) into the target cell membrane".
SARS-CoV-2 Fusion Process
Our Research Project
We are currently undergoing a Research Project called: Design of mimetic proteins that block the fusion of SARS-Cov-2 with the host cell.
S1
S1 subunit contains a receptor binding domain (RBD), which is responsible for recognizing and binding with the cell surface receptor.
S2
S2 subunit contains other basic elements needed for the membrane fusion.
Membrane
Enveloped viruses contain a nucleocapsid surrounded by a lipid bilayer which accommodates the viral membrane proteins.
Project Resume:
Design of mimetic proteins that block the fusion of SARS-CoV-2 with the host cell
The S protein of SARS-CoV-2 promotes the adhesion of the virus to the host cell through the ACE2 receptor and its fusion with the cell membrane. The mechanism of this process, common to other retroviruses such as HIV, occurs through a conformational change of the S2 subunit in which two regions HR1 and HR2 interact, bringing the membranes closer together.
Blocking this process may be a promising strategy to prevent infection or block virus replication as both regions are highly conserved in the virus genome. Our group has previously designed recombinant proteins that mimic the HR1 region of HIV-1 and strongly interact with the HR2 region, inhibiting fusion. These proteins are potent inhibitors of HIV-1 infection.
Given the homology between the structures and interactions of the HR1 and HR2 regions of SARS-CoV-2 and HIV-1 and the similarity of their fusion mechanisms, we propose to apply a similar strategy to design and produce SARS-CoV-2 HR1 mimetic proteins, characterize them and test their inhibitory activities against virus infection in cell assays. In addition to their therapeutic potential, given that the main route of infection is through the respiratory tract, these molecules could be used in nasal inhalers as prophylactic agents.
Project Progress
Progress
100%
Fresh from the Press (In the Media)
Recently published information in the media about our COVID-19 research.
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