Prof. Dimitar Dimitrov, director of the Center for Antibody Therapy at the University of Pittsburgh, USA: We were the first in the world to discover a powerful drug against the cor

Table of contents:

Prof. Dimitar Dimitrov, director of the Center for Antibody Therapy at the University of Pittsburgh, USA: We were the first in the world to discover a powerful drug against the cor
Prof. Dimitar Dimitrov, director of the Center for Antibody Therapy at the University of Pittsburgh, USA: We were the first in the world to discover a powerful drug against the cor
Anonim

Prof. Dimitar Dimitrov is the director of the Center for Antibody Therapy at the University of Pittsburgh, USA. Acquired a "doctor" degree at the Sofia University "St. Cl. Ohridski" in 1976, and a bachelor's degree in 1976

Prof. Dimitrov has worked in the US since 1990, and in 2017 he established the Center for Antibody Therapy at the University of Pittsburgh.

His main research interests are to identify and characterize novel human monoclonal /mA/ antibodies as candidate therapeutics, as well as to develop new strategies to enhance their safety and efficacy.

Recently named one of the 10 “Scientific Superheroes” by MediFind. Prof. Dimitrov is recognized on the list as one of the first to discover neutralizing antibodies for the original SARS coronavirus in 2003. In the following years, his team discovered powerful antibodies against many other infectious diseases. His laboratory recently isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus that causes COVID-19.

Regarding finding antibodies to treat COVID-19, Prof. Dimitrov points out: "When I was in my home country Bulgaria, I was fascinated by the so-called hybridoma technology and used it to produce monoclonal antibodies (mAbs) - " mono', meaning 'one', or one particular antibody with known affinity for a particular pathogen. Later, my team used an extremely powerful method called "phage display" to detect very specific, human monoclonal antibodies against many viruses, including SARS-CoV, MERS-CoV, and Hendra and Nipah viruses.

Now at the University of Pittsburgh we have discovered potent neutralizing mAbs against SARS-CoV-2 using phage display.

The COVID-19 pandemic has changed the whole world and forced us to look at medicine and scientists who are looking for and developing new ways to treat diseases that are dangerous to all of humanity”. Therefore, today we offer you the exclusive interview with Prof. Dimitar Dimitrov - antibody engineer and scientist in the field of infectious diseases, directly from the USA and especially for the readers of "Doctor".

Prof. Dimitrov, is the drug you discovered for the coronavirus infection a new formulation of a drug, or is it already known and modified?

- It's a new formula. We've managed to isolate the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19.

Tell us more about when you started working on discovering a specific drug against the COVID-19 virus? What difficulties did you have to go through?

- We managed to isolate our antibodies back in February last year. We characterized them in vitro. And on March 12th, we filed a patent for their sequences. We were probably the first in the world to discover potent, specific drugs against this virus. The big companies used a different detection method that was slower than ours and about a month behind. However, we did not have their integrated manufacturing capabilities and money, so even though we were the first to discover such drugs, we are several months behind them in producing our antibodies for human use.

How far have the drug trials gone and what results are you reporting?

- The drug is manufactured and ready for human clinical trials. Hopefully it will be able to work against some of the new variants of the virus as well.

Can it be applied to all stages of infection development?

- No, not for everyone - only for the initial stages of the infection.

One question torments Bulgarians during this one pandemic year - why have billions poured in to discover and test a vaccine against the disease, and there is deafening silence around the medicines for its treatment?

- Actually, this is not true for the US. Billions are also given here for medicines like ours. And information about them is often reported in the news.

If you had to compare the possibility of handling the pandemic with the help of vaccines and your medicine, what would be your comment?

- They complement each other. Vaccination does not work for some people and also after a person is infected, but our medicines work.

When can we expect the drug to be available in hospitals, including in Bulgaria?

- Hopefully in a few months it will be available to US hospitals. I don't know about Bulgaria - it is difficult to predict the commercial development.

Is the anti virus cocktail they treated President Trump with really that effective?

- Yes, it is very effective, just like our medicines.

Can you also share about your successes in developing other drugs against dangerous infections?

- We made a number of drugs against the original SARS-CoV, and then for MERS-CoV, Hendra and Nipah, dengue, and more. Our Hendra and Nipah antibody is used in Australia to protect and treat people from this virus, which causes up to 90% mortality.

Image
Image

What are antibodies?

Our immune system produces antibodies in response to a foreign pathogen, whether it is a bacteria, virus or fungus. Antibodies are Y-shaped blood proteins made by white blood cells called “B cells”. They neutralize pathogens by attaching to their surface and preventing them from entering human cells - signaling our immune system to clear the pathogen from our bodies.

Humans have all kinds of antibodies floating around in us at all times looking for foreign pathogens to attack. When a specific virus, such as SARS-CoV-2, infects the human body, our immune system will try to produce enough specific antibodies against it before the infection becomes overwhelming. This process can happen faster and be more successful in preventing infection if we have pre-existing antibodies against the pathogen.

Antibodies are part of us - literally. We have billions of them in our bodies, with a total weight of about 100 grams. If there are so many antibodies in our body, they must be safe and very important, right?

In fact, antibodies are probably the safest type of therapy and have many important functions. One of them is to prevent and treat infections caused by viruses. The human immune system can produce antibodies specific to each type of virus that bind strongly to it and block it from infecting our cells - so-called neutralizing antibodies.

Steps to Success

The first step of Prof. Dimitrov and his team was to identify the antibody genes from many people, then separate out those that encode only the antibody domains of interest - the so-called "variable domains". They then created a collection containing over 100 billion antibody domains of different specificity, one of which they hoped would bind tightly to the coronavirus protein.

Using a process called panning (like in Western movies where gold hunters use sieves to separate gold particles from sand), in just one week separate the weakly binding or non-binding domains from those that are bound with the target - in this case with SARS-CoV-2.

Using as bait a small part of the SARS-CoV-2 protein called the receptor binding domain, which is key to binding and infecting human cells, Prof. Dimitrov and his team "capture" and identify in their large collection of antibody domains, the one they call ab8 - it binds strongly and specifically to the spike protein.

To increase the binding strength of ab8 and ensure that it stays in the blood for a long time, they add a fragment of the antibody called Fc. This increases the size of the molecule, but is still smaller than full-size antibodies.

An antibody has a better chance of penetrating tissue the smaller it is. An antibody domain that is about one-tenth the size of an antibody is able to penetrate tissues and reach areas where the virus causes significant damage, such as the lung.

Recommended: