- 18 Oct 2020
Researchers at Karolinska Institutet in Sweden have identified a small neutralizing antibody, a so-called nanobody, that has the capacity to block SARS-CoV-2 from entering human cells. The researchers believe that this nanobody has the potential to be developed as an antiviral treatment against Covid-19. Nanobodies are comparatively lighter than antibodies and are easier to produce in bulk at a cheaper rate than polyclonal antibodies.
The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell.
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What are Nanobodies?
Researchers have used a naive llama single-domain antibody library and PCR-based maturation to produce two closely related nanobodies, H11-D4 and H11-H4, that bind to RBD and prevent its interaction with ACE2. PCR or Polymerase Chain Reactions are used in microbiology to make many copies of (amplify) small sections of DNA or a gene. Antibodies consist of two chains namely light chain and heavy chain. However, sdAbs(single-domain antibodies) are the smallest functional antigen-binding fragments of an antibody devoid of the light chain that were initially discovered in camelids(camels and llama). These are also called nanobodies and have a lesser molecular weight when compared to conventional antibodies.
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Advantages of Nanobodies over Conventional Antibodies:
Nanobodies are often compared to poly- and monoclonal antibodies and antibody fragments, and the methods used to produce these.
● Nanobodies are easier to produce cheaply in bulk than polyclonal antibodies.
● They are stable in a wide range of temperatures , remaining functional at temperatures as high as 80°C.
● Nanobodies are also stable at extreme pH levels, able to survive exposure to gastric fluid
● Nanobodies are more compatible with genetic engineering methods
● Relating to structure, there is a hydrophilic side of nanobodies that is not present in conventional antibodies. This means Nanobodies do not have issues with solubility and aggregation otherwise associated with conventional antibodies.
What's in here?...
The search for effective nanobodies which are fragments of antibodies that occur naturally in camelids and can be adapted for humans began in February when an alpaca was injected with the new coronavirus' spike protein, which is used to enter our cells.
After 60 days, blood samples from the alpaca showed a strong immune response against the spike protein.
The researchers cloned, enriched and analysed nanobody sequences from the alpaca's B cells, a type of white blood cell, to determine which nanobodies were best suited for further evaluation. They identified one, Ty1 (named after the alpaca Tyson), that efficiently neutralizes the virus by attaching itself to the part of the spike protein that binds to the receptor ACE2, which is used by SARS-CoV-2 to infect cells. This blocks the virus from slipping into the cells and thus prevents infection. Ty1 can be inoculated in the form of a drug or vaccine and administered to patients affected with Covid-19. The remedy will be highly cost-effective and will be easily available to the mass-the two basic facts that places this patent above others.
Image Credits: Chromotek
Conventional antibodies have two variable domains, called VH and VL, which offer each other stability and binding specificity. Nanobodies have VHH domains and lack VL domains and are highly stable and act as better protagonists for animal testing phase.
"Our results show that Ty1 can bind potently to the SARS-CoV-2 spike protein and neutralize the virus, with no detectable off-target activity" says Ben Murrell, assistant professor in the Department of Microbiology, Tumor and Cell Biology and co-senior author of the publication. "We are now embarking on preclinical animal studies to investigate the neutralizing activity and therapeutic potential of Ty1 in vivo".
Researchers,scientists, healthcare workers have been assiduous in the fight against Covid-19 and their diligence is getting reflected in the falling rate of newly affected Covid-19 patients. If the research proved to be efficacious in curbing widespread infection, then this could be of clinical utility in treatment planning and prognostication.