Saturday, 01 October, 2022

Biotechnological aspects for covid -19 Drug & Vaccine Discovery


Introduction

For the aspect for developing the vaccine or drug for the Covid-19 which is termed as the SARS-coronavirus. It is important to understand the structure of the virus before discovery of a drug or vaccine.

Structure

They are pleomorphic, but tend to be ovoid in shape and contains 2 subunits

(S1)Binding to host cell    (S2) fusion of viral and cellular membrane. They have spike glycoproteins on their surface which helps them in entry in the cells. Haemaglutinin esterase dimer helps in invading mechanism attachment.

Virus has a specific ability to mutate according to external condition, so it is a challenging task for the scientist to prepare a specific drug or vaccine. But according to the research at John Hopkins University it states that coronavirus mutates much slower than the flu virus .So a vaccine could prove effective for a longer period.

The SARS-2 ,COVID-19 ,virus is a type of virus that has been found in the bats as well as pigs .Initially it showed no effect to the human but on consumption of bats it became virulent to human host by amplification of its genome hence human transmission began. These type of virus get entry in human through the Naso- Pharyngeal tract and they exhibit their viral activity by binding with the ACE-2 type receptors. These type of receptors are found in lungs as well in large number in gastro intestinal lining.

The virus may contain the bat as well as pig sequence too in the bottom right of its structure with the viral attachment protein and receptor site for binding. As the virus attaches , viral effect on the host is onset within few days with the symptoms like pneumonia, palpitations, headache, dizziness , malaise, mylagia, fever typically with chills and rigors  diarrhea.

Biotech aspect for drug discovery

As per the model of the R-[0] Naught, the mortality rate can be found and its currently high. This virus has been affecting each and every countries in the world so it is very important for the research of new molecule or drug as there so far no specific treatment for this ,only supportive therapy and some Anti-virals can help upto some extent. So there are many biotech and pharma companies coming together and accelerating the discovery of drug and vaccine.

I think that potential target for developing of new drug against coronavirus, include the protease inhibitors like Ritonavir , Nelfinavir are considered as broad spectrum antivirals. To prevent processing of the RNA polymerase or cleavage of viral S  glycoprotein and inhibitors or Haemaglutinin esterase activity to limit viral replication. Antibodies against the viral s glycoprotein on unindentified receptor for SARS-COV-2 might block entry of virus.

Remdesivir is recognized promising antiviral drug against wide spectrum of RNA virus that include SARS,MERS, that is currently on clinical development for ebola. This incorporates into viral RNA chain and result in pre-mature termination .This drug has shown higher efficacy than other drugs like ribavarin, so this can be formulated and specific changes in structure of remdesivir like change in position of functional group, addition or removal of linkers as well using analogue with computer aided drug design (CADD)helps in drug discovery.

The phase trials should be successful with less potential adverse reaction, as well should be compatible with body as well other class of drugs with less drug interaction. Integrated biotech tools are used in process of protein candidate in drug discovery.

In this way biotech helps in the formulation n of new drug as well the biologist, pharmacologist, pharmaceutical scientist collaborate with biotech technician to implement appropriate strategy to synthesize biological molecule so that pharmacological and toxicological studies can be proceed.

Other than that a drug name FORSYTHIA that is derived from the plant has specific effect like antiviral so this may be a good candidate specific isolation of the active components from it can be studied under various blood cells and a potent drug can be formed . If this can be lead for the new drug then it should be accelerated progress in the animal as well clinical trials too.

BIOENGINEERED TREATMENT

Plasma convalescent therapy

This type of therapy constitutes the extraction of antibodies from the plasma of fully recovered patient from the COVID-19, due to infection from coronavirus contain antibodies that are specific for certain type of antigenic epitomes.

This plasma containing antibody is refined and concentrated crude anti toxic serum is obtained, mostly the constituent of antiviral antibodies is the Gamma globulin, process to separate antibody from plasma is termed as plasmapheresis. This isolated Gamma globulins that mainly contain IgG antibody are given to critically ill patient of same blood group as donor.

During the animal trials the antigen should be  experimented via screening techniques and after that this antigen are injected in the animal like monkey  and their body produce antibody as these virus doesn’t effect them so antibodies produced from them are collected and they can be used for developing polyclonal as well as monoclonal antibodies in this way is may be possible to cure people.

Gene therapy : A ray of hope

As gene therapy is new and relatively undefined means of treatment, compared with other treatment guideline , chemistry , manufacturing and control activities are gating factor. There are challenges with dosing, unidentified analytics, of the viral vector types open to gene therapy innovation was found that adenovirus vector have proven safe vehicle for getting genetic material into cells. This genome does not incorporate into host genome but may maintain long term expression , this maybe a hope for a new treatment .

It is really challenging compared to monoclonal antibodies, as well coronavirus may have multiple serotype both wild type as well engineered type that can be prepared using recombinant technology and they can be used as vectors with the preference for tissue being targeted.  But this tjherapy may be really tricky in this situation.   

Aspects for vaccine discovery

Vaccine is a boon for every person on the planet, as it protects us from the deadly disease. Vaccine discovery for various disease is a challenging task it takes a lots of trial and pre clinical as well as post clinical trials studies to observe its effect. First step should be as this is a novel virus this should be grown in cells in laboratory and all existing vaccine of same disease originating from this virus like SARS/MERS should be tested as well antibodies too after isolating the specific antigen.

Maybe combining the dead virus with several atrophins may result to boost the immune response and to see if there are protective antibodies are formed .Vaccine for a COVID-19 is a challenging task as first method the virus should be isolated from the infected person then this virus should be incorporated into a cell to study the effect on .After the viral genome that is decoded using the biotech method like phoretic  pattern may be useful for design a vaccine.

They may be further isolated via electrophoretic as well as HPLC and by further isolation its sequence can be known  (1) host signal peptidase   (2) viral serine protease .  This strain having virulent activity is cut of using biotech separation and specific cloning with specific plasmid maybe done to produce less virulent or hybrid clone. This Bio-engineered clone contain viral genome that can be disabled or virulence can be decreased. After that this may be cultured into the cell of kidney lungs of animal and allow it to grow well .Then this tissues are harvested and virus are obtained that have less virulence .  they may be attenuated and via nasal route immunized and as it is low virulence it doesn’t cause infection but as it contains viral genome body can produce antibodies against it.  It should be checked that virus doesn’t grow in human cell than it may be candidate for vaccine.

Other than it viral proteins can be isolated from the virus as they don’t replicate or infect , but they also don’t send out danger signal to immune response. This type of proteins can be bio- engineered and mixed with specific adjuvants to mimic inflammatory effect of infection.

It may be possible to break the virus into different component immunize with purified components clone viral gene, than it may be expressed in bacteria/virus/cell culture and purify protein. Antigen usually a capsid or membrane protein this is type of subunit vaccine. If possible to delete the bat sequence from the viral genome structure eliminates genes that code proteins linked to virulence, safe and stable attenuated strains may be produced this too may be good candidate for the vaccine.

Name of Blogger: Amin Viraj Mayur
ARPB Blogger ID: ARPBGZ275

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