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Nanomedicines Against COVID-19

Madison Pascual Munar has a Doctorate degree in Molecular Biotechnology.

Nasal Spray for COVID-19

Nasal Spray for COVID-19

Nanomedicine and Its Role in COVID-19 Pandemic

A war is raging within our cells. Scientists are on the frontlines of creating a safe and effective technology to solve insurmountable medical catastrophes like a global pandemic.

Nanomedicine is a new branch of medicine where nanotechnology and nanomaterials are being employed for disease diagnosis and treatment. Nanoparticles are designed, synthesized, and optimized to address various medical dilemmas such as cancer, neurodegenerative diseases, genetic diseases, and viral diseases. Quantum dots for instance, are nanometer size particles used for cancer detection and treatment.

Conventional production of antibodies employs the use of Llamas, Camels, or Alpacas among others. These animals were chosen because of their ability to produce antibodies which are highly similar to human antibodies. Moreover, these animals produce another set of antibodies which are observed to bind and reach places which the other antibodies cannot reach. Because these antibodies are just a fraction of the size of the normal antibodies, they are called nanobodies.

A paradigm shift from extracting bioactive compounds from plant or animal sources towards designing, engineering, and extracting nanobodies from recombinant bacteria or yeast cells were all realized in a science laboratory.

Llamas used to produce antibodies.

Llamas used to produce antibodies.

Discovery of a Potent Nanobody that Can Neutralize SARS-CoV-2

Researchers at the University of California San Francisco (UCSF) has discovered a potent nanobody (Nb) against SARS-CoV-2 upon screening their Yeast Library expressing a plethora of synthetic antibodies and nanobodies.

These nanobodies can be manufactured in bacteria (Escherichia coli) or yeast (Pichia pastoris) expression systems through genetic engineering. The genes coding for the nanobodies were sequenced, synthesized, and cloned in expression cells. The recombinant cells will synthesize these proteins at a very fast rate, which can be harvested, purified, and be used as prophylaxis against COVID-19.

Yeast (Pichia pastoris)

Yeast (Pichia pastoris)

Advantages of Producing Synthetic Antibodies Using Yeast Library

ProductionYeast Library SynthesisAntibody from Llamas

Rate

Weeks

Months

Cost

Inexpensive

Expensive

Blocking The Spike-ACE2 Interaction Through Nanobodies

SARS-CoV-2 enters the human cells via the Spike-ACE2 receptor interaction. Targeting this cell entry mechanism is the main objective of the UCSF Scientists in re-screening their readily available yeast library of synthetic nanobodies. They published a pre-print of their results in the bioRxiv Journal with the title "An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation". This technology is currently under patent licensing.

Based on their results, two types of nanobodies, Class I (Nb6 and Nb11) and Class II (Nb3), have shown extreme potency in neutralizing the SARS-CoV-2 viral particles. The nanobodies were observed to compete with the Receptor Binding Domain (RBD) of the spike protein, which disrupts the Spike-ACE2 interaction, thereby preventing the viral particles to enter the cells. Both Class I and Class II nanobodies binds simultaneously to the spike protein, hence preventing SARS-CoV-2 infection.

The neutralization activity of candidate nanobodies was validated in viral plaque assays using VeroE6 cells infected with live SARS-CoV-2 virus.

TypesNanobody (Nb)Mechanism

Class I

Nb6, Nb11

Targets RBD in spike protein and competes for ACE2 binding sites

Class II

Nb3

Targets other epitopes, external to RBS, and decrease Spike-ACE2 interaction

Scientists Behind The Discovery of Potent Nanobodies Against SARS-CoV-2

Peter Walter, Aashish Manglik, and Michael Schoof are the scientists behind the discovery of AeroNabs.

Peter Walter, Aashish Manglik, and Michael Schoof are the scientists behind the discovery of AeroNabs.

Peter Walter, PhD

Dr. Peter Walter is a Professor of Biochemistry and Biophysics and a Howard Hughes Investigator at UCSF. Dr. Walter also holds various scientific awards, which include the 2018 Breakthrough Prize in Life Science, 2015 Vilcek Prize in Biomedical Science, 2014 Lasker Basic Medical Research Award, 2014 Shaw Prize in Life Science and Medicine, and the 2012 Paul Ehrlich and Ludwig Darmstaedter Prize.

Aashish Manglik, MD, PhD

Dr. Aashish Manglik is an Assistant Professor of Pharmaceutical Chemistry at UCSF. He was awarded the Spector Award in 2008 by the Washington University. He is also one of the 30 under 30 awardee in 2013. He received the Director's Early Independence Award from the National Institute of Health. He also bagged the Young Investigator Award in the International Narcotics Research Conference in 2017.

Michael Schoof, MPhil

Michael Schoof is a Graduate student in Dr. Walter's Lab. He has a Bachelor of Science degree in Molecular, Cellular, and Developmental Biology from Stanford University. He obtained his Master of Philosophy degree in Genetics from the University of Cambridge, UK.

AeroNab Mode of Action Against SARS-CoV-2

AeroNabs-6 is A Genetically Engineered Nanobody

After discovering potent nanobodies which showed neutralization activity against SARS-CoV-2 in vitro, the team further optimized and genetically enhanced the candidate nanobodies to further improve its efficiency.

A single or monomeric nanobody (mNb6) was found to be highly potent in blocking Spike-ACE2 binding. A single amino acid substitution on the nanobody's sequence has led to a 500-fold increase in potency. They also chained three monomeric nanobodies (Nb6-tri) so that it can bind to the three Receptor Binding Domain (RBD) on the spike protein. This experiment led to a 200,000 fold increase in potency as compared to a monomeric nanobody. They called this genetically engineered nanobody with neutralizing activity against SARS-CoV-2, AeroNabs-6.

Outstanding Features of AeroNabs

AeroNabs

Stable at High Temperature (65°C)

Stable after Lyophilization

Stable after Aerosolization

Deployable

Aerosol-Mediated Delivery

Over-The-Counter

Self-Administration

Non-Invasive (Nasal Spray)

Prevents Early Infection

Breakthrough In Medical Research

Nanomedicines has been available in the market as early as 1990. Cancer is one of the diseases where nanomedicines are the drug of choice. Available treatment for cancer involves chemotherapy and radiation which are non-specific and may affect healthy cells in the body. In contrast, nanomedicines are designed to be highly specific to certain types of cancer cells to intervene on its uncontrollable division resulting in tumors. Some nanomedicines are designed to induce apoptosis or cell death to prevent further spread and metastasis of cancerous cells in the body.

Nanomedicines Available in The Market

YearNameUseActive Compound

1990

Adagen

Severe Combined Immunodeficiency Disease

Pegylated Adenosine Deaminase Enzyme

1995

Doxil

Ovarian Cancer

Pegylated-Stabilized Liposomal Doxorubicin

1996

DaunoXome

Sarcoma

Liposomal Daunorubicin Citrate

2002

Eligard

Prostate Cancer

Leuprolide Acetate and PLGH Polymer Formulation

2005

Abraxane

Breast Cancer

Albumin Protein-Bound Paclitaxel

References

Comments

Madison Pascual Munar (author) from Philippines on November 24, 2020:

Thanks for the visit Anj Agustin

Anj Agustin on August 24, 2020:

Good read. Very informative. :)