When the almost former president of the United States, Donald Trump, claimed to have recovered from covid-19, highlighted antibody cocktails as a fundamental part of his ‘miraculous’ recovery. However, lThe antibodies used to treat it have a complex structure, do not penetrate very deeply into the tissue and can cause unwanted complicationss. Also, producing antibodies is difficult and time consuming. Therefore, they are probably not suitable for widespread use, and in fact they have not become an effective treatment for COVID-19.
Antibodies are an important weapon in the defense of the immune system against infection. They bind to the surface structures of bacteria or viruses and prevent their replication. Therefore, one strategy in fighting disease is to produce effective antibodies in large quantities and inject them into patients.
Their combination, as in the case of Trump, may represent a new step in the treatment of covid-19. The last to arrive is ZD7442, a combination of two monoclonal antibodies A long-acting drug under development that is being investigated as a preventive option for people exposed to COVID-19 and to treat and prevent disease progression in patients already infected with SARS-CoV-2.
The drug, developed by Astra Zeneca in collaboration with University College London Hospitals (United Kingdom), has been shown to cause instant immunity to COVID-19 after administration.
AstraZeneca is evaluating AZD7442 in the prevention of COVID-19 in two phase III clinical trials. PROVENTwill evaluate its safety and efficacy in preventing SARS-CoV-2 infections for up to 12 months, in about 5,000 participants.
STORM CHASER evaluates the safety and efficacy of AZD7442 for prevention of post-exposure covid-19 in 1,125 people. Participants in this study will be adults over 18 years of age with potential exposure, within 8 days, to a specific individual identified with laboratory-confirmed, symptomatic or asymptomatic SARS-COV-2 infection, who therefore have a risk of developing covid -19 imminently. STORM CHASER will take place in the US and UK and the results of this trial are expected to be ready by the first half of 2021.
Early data suggest that AZD7442 appears exercise immediate and long-term protection against covid-19 for people who have been exposed to the virus. Scientists believe that it could work as an emergency treatment to prevent the onset of the disease and its progression.
On the other hand, researchers from the Karolinska Institute (Sweden) have developed new small antibodies, also known as nanobodies, that prevent the SARS-CoV-2 coronavirus from entering human cells. The study, published in “Science,” shows that a combined nanbody had a particularly promising effect, even if the virus mutated.
Specific proteins, spike proteins, on the surface of the SARS-CoV-2 coronavirus help the virus infect host cells. Therefore, antibodies that block spike proteins and prevent them from binding to the cell can be one way to stop infection.
From the perspective of possible therapeutic interventions, nanobodies may be a better alternative than normal antibodies. That’s because the nanobodies are significantly smaller. Therefore, they can bind to the virus in more areas than normal antibodies. Nanobodies also have higher stability and are easier to cost-effectively produce on a large scale.
In fact, to generate the nanobodies for this study, the researchers vaccinated alpacas and llamas, animals whose immune systems naturally produce both antibodies and nanobodies, with the coronavirus spike protein. Among the nanobodies generated by the animals, they selected the best. Among them, four were identified as exceptional in blocking the virus’s ability to spread between cultured human cells.
«My ‘favorite’ is the llama nanobody Hällberg points out. It binds directly on the surface where the virus binds to the host cell receptor ACE2. ‘
“What is special is that we have attached nanobodies that bind to two different places in the peak protein of the virus,” he explains. Martin Hällberg, one of the researchers corresponding authors of the study.
“This combination variant binds better than individual nanobodies and is exceptionally effective in blocking the ability of the virus to spread between human cells in cell culture,” they note.
Plus, they worked even when tested on an extremely fast mutating virus variant. “This means that the risk is very small that the virus will become resistant to these combined nanobodies,” says Martin Hällberg.
The researchers now hope that their nanobodies can be turned into a drug treatment as an adjunct to a COVID-19 vaccine. «They could possibly be used clinically for those who are already sick, or for prevention in people, who for one reason or another cannot be vaccinated, or who have a weakened immune system and therefore may not form a strong enough immune response after a vaccine, ”explains Hällberg.
Promising results also appear to offer therapy with interferon beta inhaOn the other hand, although it appears to increase the levels of the ACE2 protein, the key entry point of the coronavirus into cells of the nose and lungs, it predominantly increases the levels of a short version of this protein, to which the virus cannot bind.
SARS-CoV-2 enters cells in the nose and lungs through the binding of its spike protein to the cell surface protein, angiotensin converting enzyme 2 (ACE2).
Now the study, published in Nature Genetics, has identified a new short form of ACE2 and shows that, in addition to the longer form of ACE2 used by SARS-CoV-2, there is a shorter form of ACE2 that lacks the SARS-CoV-2 binding site.
Natural antiviral proteins called interferons have shown promise in the treatment of COVID-19. However, previous studies have shown that ACE2 levels increase them, casting doubt on their potential.
But the new research shows that it is predominantly short ACE2, lacking the viral binding site, that increases in response to interferons. Since levels of the longer form of ACE2 remain unchanged, interferons do not appear to drive virus entry points, supporting their use in COVID-19.
This helps explain the hugely promising results of a trial of an inhaled interferon beta treatment for COVID-19 patients. by the team of Professor Tom Wilkinson, from the University of Southampton (UK).
This research offers a fresh perspective on this short form of ACE2 and shows how it plays a very different role than the longer form of ACE2 which acts as an entry point for SARS-CoV-2.
These results will allow researchers to distinguish between these two forms of ACE2, knowledge that could prove invaluable in developing more sophisticated treatments for patients with COVID-19.