The research was published in "Science", and was conducted, among other things, under the leadership of Dr. Dina Schneidman and her team from the Hebrew University, who claims that "compared to standard antibody treatments that are currently in advanced clinical stages, which are very expensive and can easily cost over $100,000 per patient, it is possible to produce nano- Cheaply engineered antibodies, on a large scale - which is well suited to the current crisis". A nanoantibody cocktail created by the researchers in their study is currently in the pre-clinical testing phase
What saved US President Donald Trump, who was infected with Corona? Among other things, the American president received a dose of an experimental drug consisting of an antibody cocktail developed by the pharmaceutical company Regeneron, named REGN-COV2. The drug is based on a huge amount of two artificial antibodies against the spike protein on the envelope of the corona virus, which has not yet been approved by the American FDA for marketing to the general public. The treatment is considered most effective for patients who receive it at an early stage of the disease, and in Trump's case it was likely life-saving. Today, it is not possible to give such a quantity of antibodies to most patients because the pharmaceutical companies will not be able to meet the production procedures, there is not a sufficient amount of antibodies for each person as Trump received, and the cost of production may reach hundreds of thousands of dollars per patient.
Is the solution to the corona epidemic found in antibodies? Two research teams led by the American researcher Yi Shi from the University of Pittsburgh and Dr. Dina Schneidman from the School of Engineering and Computer Science and Biochemistry at the Hebrew University, developed a technology to identify nanoantibodies using proteomics (the study of proteins in the body). The technology was developed before the spread of the corona epidemic around the world, and the researchers believed after the outbreak of the virus that the technology would be effective enough to lead to a scientific breakthrough. During my research of about three months, the researchers were able to quickly produce thousands of nanoantibodies to the spikes of theSARS-CoV-2 with specificity and ability to neutralize the virus at very high rates. Using computational methods for structural modeling developed by Dr. Schneidman's group from the Hebrew University, the researchers mapped the exact location of each nanoantibody on the surface of the spikes of the corona virus, and this mapping revealed that nanoantibodies can use an abundance of new and advanced mechanisms to block virus infection. The information was first revealed in the prestigious scientific journal Science, In the article entitled "Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2".
To produce the nanoantibodies, the researchers used a llama on an alpaca farm in Massachusetts. During the study, the researchers inoculated a black female named Wally (wally, pictured on the right) with a piece of spiked protein from the SARS-CoV-2 And after about two months, her immune system produced nanoantibodies against the virus. The choice of Lemma was not accidental. All camels - camels, llamas, alpacas, vicunas and guanacos - produce antibodies similar to ours and alongside them smaller antibodies, whose molecular weight is about half that of a human antibody. These small antibodies are able to reach areas inaccessible to large antibodies like ours, and work more effectively. The complex task was to identify within the found nanoantibodies those with the best neutralizing ability to fight the corona virus. The researchers also tested camels, which are now known to live peacefully with the MERS virus, a "cousin" of theSARS-CoV-2, And they discovered that they too produced a large amount of nanoantibodies against the virus relatively quickly.
"In this study, we wanted to test the nature of the nanoantibodies, after the normal antibodies led to promising initial results when they were given to humans who were sick with corona. On the other hand, the cost of creating the antibodies was sky high and their production quantity was limited. In this study we discovered that the nanoantibodies, which are much smaller than human antibodies, have very promising antiviral activity against SARS-CoV-2. They stop the progress of the virus, do not allow it to enter the lung cells and give the immune system time to act and fight the virus", explains Dr. Schneidman. "It turns out that you can get thousands of nanoantibodies from one animal, and take them out to use them for humans. The difficulty was to identify and find the antibodies that effectively neutralize the virus from among them, because in the past there were nanoantibodies that were found to bind to the spikes of the new corona virus, but they quickly detached from them and did not prevent these viruses from infecting cells."
Accurate structural mapping carried out by the researchers to the nanoantibodies created in the studied animals enabled the engineering of a new nanoantibody cocktail that is able to cover the spikes of the corona in several places, thus preventing the virus from developing resistance to antibodies with the help of mutations. In collaboration with Prof. Paul Duprex Director of the Pittsburgh Center for Vaccine Research (CVR), the researchers revealed the nanoantibody cocktail created for the virus SARS-CoV-2, And they found that using a fraction of a nanogram (1/1000000000 gram) of the drug neutralizes viral particles sufficient to infect a million human cells. That is, their low dose is enough to neutralize the corona virus.
The researchers also found another advantage in using the new nanoantibody cocktail they assembled. Beyond the fact that it is not necessary to invest a lot of money and time in the production of a large number of antibodies as in the past, in a potential future treatment the researchers believe that it will be possible to inhale these nanoantibodies directly into the lungs, rather than by infusion. The researchers purchased a simple-to-use inhalation device, which is used against respiratory diseases (see the picture below), and found that the nanoantibodies survive intact and remain active after passing through the device. The significance of this is great - people who feel unwell and fear that they have been infected with Corona will be able to quickly go to the pharmacies closest to their home, get a nano-antibody device against Corona that will help introduce the cocktail into their lungs, without going to a hospital and burdening the health care system.
The nanoantibody cocktail is currently in preclinical animal testing. "So far the results of these tests are promising, but we are only at the beginning of the journey", says Dr. Schneidman happily. "Such treatment can be life-saving if given at an early stage of the disease to a patient in a risk group. It is a treatment that can be done, fast and convenient. People who will be exposed to confirmed patients will be able to use this treatment also as a prophylactic (preventive) treatment."
Along with the incredibly high antiviral activity obtained from the cocktail, the nanoantibodies showed excellent medicinal qualities. They were found to be very stable and able to stay at room temperature for at least six weeks. "Compared to standard antibody treatments that are currently in advanced clinical stages, such as antibodies that President Trump received from Regeneron, which are very expensive and can easily cost over $100,000 per patient, engineered nanoantibodies can be produced cheaply and on a large scale in bacteria. This corresponds well with the needs of the current crisis", concludes Dr. Schneidman.
More of the topic in Hayadan:
One response
sounds interesting.
A review of other antibody studies is somewhat lacking.