How COVID-19 virus attacks human cells:
The COVID-19 pandemic emerged as a severe threat to human health. It is caused by coronavirus 2 virus (SARS-CoV-2). Coronaviruses are positive-stranded RNA viruses, featuring the largest viral RNA genomes known to date (27-31 kb). The coronavirus surface presents a trimetric S protein consisting of N-terminal S1 and C-terminal S2. The S1 consist of N-terminal domain (NTD) and C-terminal domain (CTD). The CTD is the receptor binding domain (RBD). The RBD is responsible for binding to host cell surface ACE2, the S2 for binding of host protease TMPRSS2. Thus, S protein is the key for COVID-19 virus entry into human cells
Why Spike (S) proteins is the vaccine development target?
Spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. To stop SARS-CoV-2 infection, one strategy is to block the virus entry human cells, i.e to interrupt the binding between virus and human receptor ACE2 or TMPRSS2. Researchers try to raise antibodies targeting at S1 protein or at RBD epitopes. Those antibodies prevent virus from binding to human ACE2. Therefore, S protein is the target for vaccines, therapeutic antibodies, and diagnostics.
How COVID-19 vaccine made and Will COVID-19 vaccine work?
As we know there is barely any specific antivirus medicine, a vaccine is widely regarded as the best path to fight virus outbreak. In the case of COVID-19 virus, tremendous effects are focused at the vaccine targeted at S protein. Many methods are used in COVID-19 vaccine development, like (1) tradition method using purified S protein antigen, (2) Adenovirus based by inserting the codon sequence of S1-protein into Adenovirus; (3) DNA vaccine using the double-stranded DNA embedded S-protein, (4) mRNA vaccine using the mRNA of S1-protein, (5) or use the inactivated COVID-19 virus. No matter what method used, the goal is the same, to raise the specific antibody again S protein. That antibody binds S protein which prevent the virus bind to human receptors, ACE2 or TMPSS2.
The antibodies specifically recognize the accessible epitopes of S protein that used in vaccine development. As RNA type virus, COVID-19 tend to have more mutation during its replication. Luckily, research found there are no many mutated S (spike) protein than anticipated so far. The original identified mutated S in China is D614 and later on G614 in UK and North America. Such mutation increases its infection rate (enhance its bind affinity to human ACE2), but seem still can be recognized the wild-type vaccine antibody, which is good news.
The question is, if we have a safe and effective COVID-19 vaccine, how long its antibody last in human body? Some virus’ vaccine provides a life-time protection. Most likely, it is not the case for COVID-19. Currently, developing an effective vaccine, validating its duration and effectiveness become arm race worldwide.
Gentarget’s products facilitate COVID-19 vaccine development
Gentarget developed lentivirus products that express, human ACE2 (CAT#: LVP1310), TMPRSS2 (CAT#: LVP1309), carrying a internal Red fluorescent marker (RFP) for monitoring the lentivirus’s transduction rate, and carrying the Blasticidin antibiotic selection for stable cell line generation.
Gentarget also provide the ready-to-use lentivirus expressing the full length COVID-19 S protein (CAT#: LVP1329) and S1-RBD domain (CAT#: LVP1330). They express the humanized full-length S protein (~140 kDa) or S1-RBD (~45 kDa), carrying a poly-histidine tag at the C-terminus 6His tag.
Simply add the lentivirus into any desired mammalian cells, your cells will express the target and you can use the cells for any cell-based assay or detection. You can also purify the mammalian expressed S protein or S1-RBD domain via Ni NTA affinity column (6His) and use them as antigens in antibody development or validation, ELISA plate detection and so on.
To present COVID-19 S protein as its native surface conformation, Gentarget also make the Viral-Like-Particle for S protein (CAT#: LLP001) and stable cell lines expressing human ACE2 receptor.