CAN CHICKEN EGG-YOLK ANTIBODIES (IgYs) BECOME A POTENTIAL SOURCE TO TREAT COVID-19?
Momina Suleman Ghanchi
Biotechnology graduate | Eager to work in the field of Microbial Genetics, Clinical Microbiology, Molecular and Cellular Biology, Molecular Pathology, Genetic Engineering, Virology, Biochemistry & Drug discovery
No one can ever forget the sense of scorching and quavering situation of when the tiniest and invisible creature embarked on its journey to devastate the world economically, environmentally and psychologically. That ferocious beast was first observed in the city of Wuhan, Hubei Province, China on December 31st, 2019. Later on, the disease spread like wildfire into over 210 countries. Scientists were badly hustled by this uncontrollable and merciless living entity. Insufficient resources was an overriding concern for the already underdeveloped regions across the globe. The flow of blood along the nerves in each individual got interrupted, economy sliding down, disconnection between the heart and the brain generated absurd thoughts among humans, be it a professional or a layman, but that unflinching determination of our heroes to jeopardize their lives to save the bacon of humanity will always be applauded until the last breath of the earth planet. In medias res, myriads of clinical trials were carried out to cast light on the potential treatment against COVID-19.
Everyone desired to crawl out of their skin. People were hovering to get the suitable and revitalizing intervention. A huddle of candidate drugs was studied with emphasis on the use of anti-malarial and anti-viral drugs, and different forms of oxygen therapy.
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ANTI-MALARIAL DRUGS
The delphic and enigmatic letter by Chinese researchers birthed the idea that Chloroquine and hydroxychloroquine would deliver the goods. The whole world was on cloud nine until the researchers from the US blew the whistle on the use of these medications on April 21, 2020, hammering into the head of the medical staff and the general public the life-threatening side effects such as, QT prolongation, retinal damage, hypoglycemia, and hemolysis of blood in patients with G-6-PD deficiency.
ANTI-VIRAL DRUGS
The flickering lights suddenly turned into the blazing sunshine when the scientists added tang to their research after exploring all avenues to have REMDESIVIR approved by the FDA. Ritonavir-boosted nirmarelvir (Paxlovid) is also strongly recommended by the COVID-19 Treatment Guidelines Panel followed by REMDESIVIR. Molnupiravir is the least recommended drug, or say, on a few occasions.?The use of medications and the entire treatment for non-hospitalized children possess different school of thought. The same can be observed in hospitalized patients. To halt viral RNA synthesis, Remdesivir rains on its parade by serving as an adenosine analog resulting in an incomplete strand of nucleic acid of the virus.
CONVALESCENT PATIENT PLASMA
?Having squeaked through the clinical trials, researchers made a saccade to convalescent plasma as a potential treatment option. The convalescent plasma obtained from the recovered patients afflicted with COVID-19 encompasses antibodies that grasp the virus as an eagle preys upon with its sharp talons. The FDA has issued Emergency Use Authorizations with respect to the use of high-titer COVID-19 convalescent plasma. The evidence on its use in immunocompromised patients is currently thin on the ground. ?
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PRODUCTION OF EGG YOLK ANTIBODIES (IgYs)
BACKGROUND INFORMATION
SARS-CoV-2 contains spikes on its surface as can be visualized in solar corona, which are formed of homotrimeric glycoprotein. The authors in the publication ‘THE CONVERSATION’ states that ACE-2 or angiotensin converting enzyme-2 is a proteolytic enzyme that breaks down larger protein, Angiotensin, into smaller proteins that can perform their regulatory and modulatory functions in the cells and tissues. ACE-2 is found in epithelial cells of many cell types and tissues including the lungs, heart, blood vessels, kidneys, liver and gastrointestinal tract. Binding of SARS-CoV-2 to the host cell is facilitated by these ACE-2 receptors, which is followed by viral membrane fusion and subsequent viral genome entry into the host cell. With the discovery of binding ability of SARS-CoV-2 to its host cell, scientists turned the whole situation around to reduce the snowball effect of this pandemic and claimed that neutralizing antibodies can show promising results in the treatment against COVID-19 by attaching to the spike glycoprotein of SARS-CoV-2. Although the rapid progress has been made in the scientific technology, the production of monoclonal antibodies is still challenging economically and as per the present needs of the medical practitioners. Therefore, the researchers from the two different cities, Suzhou and Beijing, of China put overwhelming effort to get around the complexity in the production of neutralizing antibodies against the spike protein of the virus. ?
Egg yolk contains predominantly immunoglobulin Y (IgY) as part of immune response. Egg white accommodates immunoglobulin A and immunoglobulin M. Past literature has documented the use of egg yolk antibodies (IgY) against different types of diseases, for instance, tetanus and diphtheria. According to China Veterinary Pharmacopoeia, IgY formulations have been prepared to cure several veterinary illnesses such as duck plague and goose plague. Human viral infections such as influenza virus, coxsackie virus, respiratory syncytial virus have been treated with these antibodies. These Egg yolk antibodies have sparked interest of functional foods. They possess certain characteristics i.e. high yield, low cost, stable chemical properties. The preponderant fact of employing IgY antibodies is that it neither binds to the human rheumatoid factors nor stimulates the human complement factors, thereby mitigates the induction of inflammation. Past study highlighted the use of anti-SARS CoV IgYs extracted from Chickens that were immunized with inactivated SARS-CoV. Researchers found that neutralization of SARS-CoV by IgY antibodies has taken place both in vitro and in vivo.
Now, it’s time to have the best of both worlds, sustainable production of IgYs and sophisticated treatment option for COVID-19. Scientists have solved the mystery by making production of anti-spike-S1 IgYs practical in chickens that were immunized with the S1 domain of the SARS-CoV-2 spike protein, which was then followed by determining their ability to neutralize SARS-CoV-2 pseudovirus using Hela cells with overexpressed human ACE2. They used eight different coronavirus spike protein mutants (including seven SARS-CoV-2 spike proteins and one SARS-CoV spike protein) for interrogating the competitive binding ability of these antibodies to these protein mutants. ??
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METHOD SUMMARY?
领英推荐
FROM CLIMBING THE WALLS TO OVER THE MOON
Astonishingly, the researchers found maximum inhibition of 75.86%. They also claimed that the anti-(SARS-CoV-2) IgYs possess neutralizing activity. The high IC50 value (270.5 μg/ml) for the anti-(SARS-CoV-2) IgYs compared to the previously studied monoclonal antibodies expresses the specific recognition of very small number (only 10%) of IgYs to SARS-CoV-2. Another shortcoming observed was lower strength of IgYs with neutralizing activity. Therefore, it has been suggested by the researchers that neutralizing activity can be enhanced by having multiple sites on the IgYs.
As far as the results of competitive inhibition are concerned, Anti-(SARS-CoV-2) IgYs indicated distinguishing competition with ACE2 in binding both the wild type SARS-CoV-2 and SARS-CoV spike proteins. Astonishingly, all the six SARS-CoV-2 spike protein mutants?(W436R, R408I, N345D, V367F, N345D/D364Y, and the more dominant mutant D614G) were competitively inhibited by the IgYs.
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SUMMARY
In a nut shell, remarkable neutralizing potency of the anti-Spike-S1 IgYs was observed against SARS-CoV-2 pseudovirus, various S mutants, and even SARS-CoV in vitro. However, further research and clinical trials are needed to determine the efficacy and safety of IgYs in treating COVID-19. According to researchers, preparation of aerosol or spray formulations for the respiratory tract, the oral cavity, and even the digestive tract seems a worthwhile strategy as it might halt the SARS-CoV-2 viral invasion through the natural infection route. At last, a combination of active and passive immunization tools, drug therapy and other precautionary measures will prove great initiative for long-term control of the SARS-CoV-2.??