BREAKING NEWS
Source: COVID-19 Drugs  Jul 19, 2021  3 months ago
BREAKING! Study Finds That N-Acetylneuraminic Acid And Its Analogs Can Be Used To Prevent Adverse Reactions Due To COVID-19 Infection Or Vaccines
BREAKING! Study Finds That N-Acetylneuraminic Acid And Its Analogs Can Be Used To Prevent Adverse Reactions Due To COVID-19 Infection Or Vaccines
Source: COVID-19 Drugs  Jul 19, 2021  3 months ago
A new study by biotech researchers from Hangzhou-China involved in a development of new drug formulation has found that N-Acetylneuraminic Acid (NANA)  and its analogs such as acetylneuraminic acid methyl ester (NANA-Me) are able prevent and also treat adverse reactions caused by COVID-19 infections and also by COVID-19 vaccines.

Edible Bird's Nest- A Good Source Of N-Acetylneuraminic acid 

It has been discovered in a past study by the same study team that certain anti-spike antibodies of COVID-19 and SARS-CoV viruses can have a pathogenic effect through binding to sick lung epithelium cells and misleading immune responses to attack self-cells.
 
The team had termed this new pathogenic mechanism as “Antibody Dependent Auto-Attack” (ADAA).
 
The study team decided to further explore a drug candidate for prevention and treatment of such ADAA-based diseases.
 
They identified an active ingredient for the drug formulation, in case being N-acetylneuraminic acid methyl ester (NANA-Me), an analog of N-acetylneuraminic acid.
 
N-Acetylneuraminic acid (Neu5Ac or NANA) is the predominant sialic acid found in human cells, and many mammalian cells. Other forms, such as N-Glycolylneuraminic acid, may also occur in cells.
 
This chemical residue is negatively charged at physiological pH and is found in complex glycans on mucins and glycoproteins found at the cell membrane. Neu5Ac residues are also found in glycolipids, known as gangliosides, a crucial component of neuronal membranes found in the brain.
 
Along with involvement in preventing infections (mucus associated with mucous membranes ie mouth, nose, GI, respiratory tract), Neu5Ac acts as a receptor for influenza viruses, allowing attachment to mucous cells via hemagglutinin (an early step in acquiring influenzavirus infection).
 
N-Acetylneuraminic acid can be found in high proportions in bird’s nest, a delicacy in East Asia.

N-acetylneuraminic acid methyl ester or NANA-Me acts through a unique mechanism of action (MOA) which is repairment of the missing sialic acid on sick lung epithelium cells. This MOA can block the antibodies’ binding to sick cells, which are vulnerable to pathogenic antibodies.
 
The study’s in vivo data showed that the new drug formulation significantly reduced the sickness and deaths caused by pathogenic anti-spike antibodies.
 
The team found that the formulation had the potential to prevent and treat the serious conditions caused by pathogenic antibodies during a COVID-19 infection.
 
In addition, the formulation had the potential to prevent and treat the adverse reactions from COVID-19 vaccines because the vaccines can induce similar antibodies, including pathogenic antibodies.
 
According t o the study team, the formulation involving N-Acetylneuraminic Acid (NANA) and its analogs such as acetylneuraminic acid methyl ester (NANA-Me)  will be helpful in increasing the safety of the vaccines without reducing the vaccine’s efficacy.
 
Compared to existing antiviral drugs, the formulation has a unique MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.
 
The study findings were published on a preprint server and are currently being peer reviewed.
 
Antibodies elicited by natural infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or by vaccines against coronavirus disease 2019 (COVID-19) may sometimes exert a deleterious effect on the individual. https://www.researchsquare.com/article/rs-612103/v2
 
Such pathogenesis of these adverse effects remains unclear, and safe effective therapies are also woefully lacking.
 
The study findings describe the promising results of a new drug candidate in combating the illness caused by the binding of COVID-19-specific antibodies to infected cells.
 
Dr Huiru Wang from Huirui Biopharma, Co., Ltd-Hangzhou, told Thailand Medical News, “Compared to existing antiviral drugs, the formulation has a unique mechanism of action or MOA of targeting receptors, broad spectrum of indications, excellent safety profile, resistance to mutations, and can be easily produced.”
 
It has been found that in many cases, recovery from COVID-19 is followed by weeks or months of a lingering illness, a condition that is commonly referred to as long COVID. These ‘long-haulers’ find it difficult to cope with daily life or work demands.
 
COVID-19 vaccines have been hailed as the only way out of the COVID-19 pandemic; however many vaccines have been associated with adverse reactions and even deaths in a few rare cases. If there was a way to treat such reactions, vaccines would be much more appealing to those who are vaccine-hesitant.
 
The research team of the current study previously reported a mechanism of SARS-CoV-2 infection whereby some anti-spike antibodies target host cells, which initiates an auto-immune process. This triggers serious consequences, including the deadly acute respiratory distress syndrome (ARDS) and the well-known cytokine storm that indicates a dysregulated immune-inflammatory response. https://www.researchsquare.com/article/rs-612103/v2
 
Alarmingly in many cases, this reaction causes the death of the patient. Dubbed “Antibody-Dependent Auto-Attack (ADAA)” by these scientists, ADAA depends entirely on the activity of the spike-specific antibodies. In fact, pregnant mice have been shown to miscarry, or have stillbirths or neonatal deaths, when exposed to anti-spike COVID-19-induced antibodies.
 
The human cell membrane is rich in sialic acid (SA), which masks the cell surface antigens to allow for self-recognition or immune tolerance of self-antigens. The loss of SA causes autoantibodies to form, which can contribute to the activation of an immune response.
 
The SARS-CoV-2 coronavirus has been shown to possess a receptor-destroying enzyme (RDE) that strips SA from the lung epithelial cells. Replacing these SA residues would thus block the autoimmune process and prevent the binding of pathogenic antibodies to these vulnerable cells.
 
The study team developed an SA analog for this very purpose. To this end, the current study reports its efficacy in preventing and treating adverse reactions caused by this mechanism.
 
Typically a successful SA analog is determined by its ability to enter the cell and participate in building a carbohydrate chain. Natural SA cannot do this, as it undergoes rapid breakdown in vivo. The scientists, therefore, chose to use N-acetylneuraminic acid methyl ester (NANA-Me) as their SA analog.
 
N-acetylneuraminic acid methyl ester or NANA-Me is an N-acetylneuraminic acid (NANA) analog that is often preferred over NANA for its cell entry capabilities.
 
However, NANA-Me is unstable at a neutral pH and requires environmental conditions to be more acidic, at a pH of around 4-4.5.
 
The study team therefore designed a formulation with NANA-Me:NANA in the 2:1 ratio called BH-103.
 
Importantly when cultured with lung epithelium cells, this compound increased SA levels on the cell surface in a dose-dependent manner, unlike those treated with NANA. This ratio was also seen to be optimal for the repair of SA-poor cell surfaces.
 
Sialic acid or SA loss was artificially induced by exposing the cells to neuraminidase or sialidase. When these injured cells were then treated with BH-103, SA levels were found to be significantly higher as compared to controls. Thus, this in vitro experiment showed that BH-103 may be able to increase SA levels in damaged cells and ultimately prevent the autoimmune phenomena from occurring to reduce disease severity.
 
It is already known that viral entry of SARS-CoV-2 depends on spike-mediated viral engagement with the angiotensin-converting enzyme 2 (ACE2) host cell receptor, via the spike receptor-binding domain (RBD).
 
Utilizing recombinant SARS-CoV-2 RBD, the study team found that treatment with BH-103 improved SA levels on exposed cells as compared to controls. Simultaneously, however, the exposed cells had lower levels of spike-RBD compared to controls.
Interestingly when neuraminidase- or sialidase-treated cells were cultured with this compound, SA levels fell, but less than that which was observed in untreated cells. However, the spike-RBD binding to the treated cells was reduced by almost 90%, despite the SA loss. In other words, the compound reduced virus binding.
 
Dr Wang added, “This result indicated that replacement of NANA by NANA-Me induced a structural change or chemical modification of the viral receptor. BH-103 not only repaired the missed sialic acid but also significantly decreased the binding affinity of the COVID-19 S-RBD simultaneously.”
 
Utilizing a mouse model, the study team injected spike-specific antibodies into pregnant mice twice a day every three days, on days 15 and 18, respectively. The mice were also treated with BH-103 just before or along with these antibody injections.
 
Interestingly BH-103 was again found to significantly reduce the rate of disease and fatality induced by the pathogenic antibodies.
 
This was confirmed by the significant histologic improvement seen in the mouse organs including the lungs, kidneys, heart, and brain, as compared to the control mouse pups. BH-103 is therefore able to prevent and treat inflammatory injury to multiple organs induced by pathogenic antibodies to SARS-CoV-2.
 
It was found that cytokine levels in the treated mouse pups were also lower than in the controls, though higher than normal. This data indicates that the use of BH-103 is also able to mute the cytokine storm caused by the virus.
 
The study findings found that the novel drug candidate BH-103 appears to be effective in repairing SA loss through the use of a unique mechanism of action to modify the virus receptor. Through this mechanism, BH-103 is capable of reducing binding affinity, while simultaneously remaining stable under neutral environmental conditions.
 
These study findings suggest that this formulation may be developed into a useful drug to prevent and treat disease caused by COVID-19-related antibodies.
 
In addition, the MOA of BH-103 may have a broad spectrum of efficacy, as it acts on all viruses that share this receptor and is not easily blocked by escape mutations. In addition, BH-103 appears to reduce multiple symptoms traceable to ADAA, including cytokine storm in the acute phase and long-haul symptoms in the later phase of convalescence. Vaccine-related adverse effects and autoimmune manifestations related to COVID-19 are also addressed.
 
Importantly the safety of BH-103 appears to be established in animal models. This compound is also easily scalable on a commercial basis, as it is associated with a simple and rapid manufacturing process.
 
Dr Wang concluded, “Therefore, BH-103 will provide an effective resolution for the urgent clinic unmet of the COVID-19 pandemic and the other possible pandemic emerging in future.”
 
For more about using N-Acetylneuraminic Acid (NANA) and its analogs such as acetylneuraminic acid methyl ester (NANA-Me) to prevent and also treat adverse reactions caused by COVID-19 vaccines, keep on logging to Thailand Medical News.
 
 
 
 

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