Development of Protein Nanoparticles for SARS-CoV-2 Virus Neutralization
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First identified in 1960, now known as coronavirus is an RNA virus where ‘corona’ stands for the crown in Latin representing the spikes present in the envelope. These viruses lack ribosomes and are inactive when subjected to the environment. Till now there are 7 known human coronaviruses. The SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2) virus outbreak at Huban Provision on January 7, 2020, in China, causing the disease COVID-19(CoronaVirus Disease-2019). The virus enters through the mediated fusion of spike protein of viral spike(S) and ACE2 (Angiotensin-converting enzyme 2) receptors on the host cells expressed by nasal ciliated cells, pneumocytes, exocrine pancreas, intestinal tract, seminal vesicle, epididymis, proximal renal tubules, heart muscle, and thyroid gland. The RNA polymerase responsible for replicating the virus's genes usually doesn't have proofreading abilities, which causes RNA viruses to have significantly higher mutation rates than the host's DNA-containing cells, up to a million times greater. Thus coronaviruses make it challenging to create vaccines.
Till now, Monoclonal antibody therapy has been an efficient treatment for COVID-19 patients. High-affinity monoclonal antibodies (mAbs) are developed by utilizing the B-cells of COVID-19 patients by phage display method. However, monoclonal antibodies cleave the body fast and shortly hold the antibodies in the lungs. Also, a high density of inhibitory domains is necessary to achieve maximum blockage efficiency in treating COVID-19.
Due to this researchers have developed a protein nanoparticle inspired by the formation of amyloids, which are identified as neutralizing the SARS-CoV2 virus. These highly ordered proteins cause a rare disease that occurs when amyloid builds up in organs. These are also associated with diseases (including PrP prion, Alzheimer's, and Parkinson's) and biological function.
To develop this new proposed nanoparticle, researchers have used the natural ability of sup53 protein's soft amyloid core (SAC) to self-assemble, which is fused with 2 protein mini binders namely LCB1 and LCB3 (Long chain base biosynthesis protein 1 and Long chain base biosynthesis protein 3). LCB1 and LCB3 are formed through three helices, making them stable and able to establish multiple contacts with viral proteins. Developed pure and homogeneous spherical nanoparticles can block the interaction between the spike-RBD protein and the ACE2 receptor present in the host. Researchers have referred to this compound as OligoBinders.
Oligo Binders are novel particles that block the entry of SARS-CoV-2 in human tissues due to their biocompatibility, stability, efficacy, and ease of production, purification, and assembly. These make them a valuable alternative for preventing the manifestation of the virus in the human body.
RERERENCE
Molood Behbahani Pour et al, OligoBinders: Bioengineered Soluble Amyloid-like Nanoparticles to Bind and Neutralise SARS-CoV-2, ACS Applied Materials & Interfaces (2023). DOI: 10.1021/acsami.2c18305
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