#BiotechNext : Post COVID Effect On Biotechnology Research: Challenges And Opportunities

Student contributors: Rudranil Samantha and Rumale Das (B. Tech Biotechnology)

The coronavirus disease 2019 (COVID-19) has caused a challenging situation all over the globe. From health to the economy, everything has been massively affected by this pandemic. People across the globe have been going through tough conditions. Control measures namely social distancing has been initiated by the governing body of every country to diminish the pace of this virus transmission. All things including science have been paused but biotechnology research is a key to fight off this pandemic by developing a vaccine, drugs. Though most of the research work has been stopped or delayed but biotechnology research is an essential field for the advancement in developing the treatment of this disease. Most of the countries are going through the lockdown phase, for which all schools and colleges regular classes are being held over the online portal. Most of the educational institutes are organizing a webinar to enhance the knowledge of each student. However, some of the researchers have been benefited due to these massive changes that have begun with COVID-19. Researchers can complete their leftover manuscript, can actively take part in some research activity and most importantly they can contribute their thoughts in developing vaccines, monoclonal antibodies, etc and also finding a solution for this deadly situation. But these may create several troubles such as the presence of limited staff for conducting a research work as to maintain social distancing, again limited technician staff for operating several types of machinery such as mass spectrometry, scanning or transmission spectrometry, etc. along with staffs those are working in supply stores. However, the chief researcher may also face some problems in losing some of his/her staff, because those may have poor immunity or some of them may be aged or some may suffer from chronic disease. Yet, this specific pandemic is driving individuals to rethink their jobs as researchers. Regularly, we are lucky enough to have the option to appoint a portion of our for family-related duties to other people viz. childcare, household works, etc; in any case, this lockdown situation has upset these basic assets and imperiled our work, as we can’t shuffle between work and home conditions. For instance, right now, a huge number of specialists, graduate students are occupied with regulating their students for their everyday training, as distance learning has transformed guardians into full-time instructors. But in some other countries like Mexico, this may be gender-based so, the research project is destined to be either scaled back or then again constrained, consequently including some pressure components to the workplace. It is to be noted that in this current scenario, it is very much effective to come up with some alternative project work related to biotechnology which guarantees to become a success. This situation has forced to change the role of chief scientists, technician and other staff members of a laboratory, whereas, on the other hand, they had also benefited with advantages such as in analyzing the leftover data, to write dissertations and also explore some new ideas in the field of bioinformatics, in silico studies, etc. Besides this, some of private industries or institutions are conducting webinars where they can gather new knowledge or technology or in some context they can also be a speaker of a certain webinar where they can illustrate their new ideas on discovery or projects or experimental work. Therefore it is a good opportunity for the upcoming or new researchers to gain knowledge or grow new abilities and thoughts to make the best out of these circumstances.

Nevertheless, these work-related deeds will be tackled with the same commitment and proficiency under this current situation, if it is thought then it would be very wrong. It is known that personal isolation and correlated tension to this pandemic in which we are now living, can have an acute psychological effect. In this situation, we all have to be extremely self-stimulated, and also we have to inspire others to be productive. As well as we all have to realize that it is not possible to concentrate on work at an equal level while someone would under normal circumstances. This situation has also raised the problems of some members of the research group to think of their financial condition or course of events for finishing a degree and future employment possibilities.

Though in some of the countries, the trajectory path of this pandemic is beyond the control line, but designs are in progress to move back to their normal activities. But it is to be kept in mind that SARS-CoV-2 will remain as a seasonal pathogen until and unless there is an effective vaccine. This situation has able to make us habituate with a new strategy which will permit us to more readily adapt to such a circumstance later on.

This COVID-19 pandemic situation has able to serve several aspects in the fields of biotechnology. The researcher has got a chance to experiment with the process of new findings and also this situation helps the professional youth to gain a vast knowledge of new technology or protocols. The students also have got a chance in broadening their knowledge in this field by writing various review papers, hand-on training, etc. Other than the specialized parts or technical aspects of leading biotechnology research, it also motivates the researcher and also the human spirit by providing spontaneity, intelligence, a positive attitude, and liberality. All the people are in a tough situation with an insecure destiny but it also offers a scope to reconsideration how can we interact with each other in a way which will good for the huge scientific province for a lengthy period. However, from this pandemic situation, the governing members of countries have also realized the importance of the biotech sector, as the key ingredients to fight against this pandemic can only be provided by this sector. On the other hand, there is a huge demand for the antibody, drugs, and other clinical items, which is rising exponentially so, this could be a factor that can trigger the development of the biotech industry at a noteworthy level. Biotechnology is gaining importance day by day. Coronavirus has given several good opportunities to researchers but there are some challenges as well, which should not be ignored.

AGRICULTURE: A SCIENTIFIC ART OF CULTIVATION

Student Contributor: Sulekha Roy (B. Sc Biotechnology 4th semester)

Indian agriculture is undoubtedly the biggest livelihood giver. Sustainable agriculture helps for comprehensive development as it contributes very significant value to the GDP. The agriculture sector is gaining importance regarding food security, environmentally sustainable technologies followed by the scope for employment.  Such environment sustainable technologies include conservation of soil, management of sustainable natural resource as well as protection of biodiversity. Indian agriculture and its related activities all together had seen a green revolution, a yellow revolution, a white revolution, and many more. India has diverse climates where we can grow different types of the crop at the same time of the year on different locations.  Our nation is blessed to have such geographical variations we are not dependent on particular weather.

 

            Let’s discuss what agriculture is all about. As we all know that science is a kind of art or in other words, science is a combination of art with logical thinking and creativity. So we can say agriculture is the scientific approach, art of cultivating plants and rearing livestock. It includes farming in all of its sectors which includes growing and harvesting crops and livestock. Also, agriculture was an opening door in the emergence of humans and opened a new area of interest in science. Now a day so many scientific tools and techniques involved in agriculture used to improve plants, animals, and microorganisms.  The implementation of biotechnology in agriculture is known as Agricultural Biotechnology. Through biotechnology, a scientist can customize the crop plant by identifying specific traits. Technology has indeed played a role in developing the agricultural sector. These technologies modernized the agricultural field India has experienced numerous revolutions to substantially improve and increase productivity, food demands, and crop growths without associated with any ecological or social harm. The green revolution brought immense change in all sectors of agriculture giving it an all-new approach.

 

            While the Gene revolution, in which a global and agriculture research system disease-free planting material, and produces crops that resist pest or disease and decreases the uses of chemicals that are harmful to the environment and humans also. The journey from green to gene revolution has seen enormous growth in agriculture techniques, irrigation patterns, and a different scientific approach. The biotechnological tools that are important for Agricultural biotechnology:

(a) Conventional plant breeding

(b) Tissue culture & Micropropagation.

(c) Molecular Marker

(d) Genetic engineering

(e) Molecular diagnostic.

Scientists provide a set of tools which is incorporated suitability with other technologies that can get implemented for the sustainable development of agriculture and food industries. As with each passing of the year, the population is increasing food is becoming one of the top priority, thus with an increasing demand for foodstuff, better quantity and better quality yield are necessary.

 FUTURE OF AGRICULTURE

            We face numerous challenges with the growth of the population, with the climate crisis. The Earth population is presumed to grow to 9.7 billion over the next 30 years. That’s a lot of individuals to feed, especially when we consider the vast hunger issue the world face today. More than one-quarter of the planet’s population that is around 7.5 billion people suffer from malnutrition, nearly are 1 billion are hungry.

 

HOW TO BE A FOOD PROVIDER TO THE PLANET OF NEXT GENERATION?

            If we want to be food providers for the world of next-generation, the next 40 years we need to produce the same amount of food as we did over the last 1000 years.  The real secret is sustainable production which should be with fewer inputs, less water, with less fertilizer, fewer pesticides moreover this also needs to be viable. To address this enormous issue of food security agriculture system requires new approaches and techniques, which can not only increase productivity but also ensure environmental protection and conservation of limited natural resources. We can go for many techniques as follows:

Enhanced hybridization– To imprint the quality and quantity of crop products.

Farming desert– Proper usage of barren lands to cultivate appropriate crops with various irrigation systems.

Continued digitization– Self-driving tractors, robots, and drones operated by a farmer’s mobile phone or tablet will enable farming round the clock during unfavorable seasons. Artificial intelligence, satellite imagery, and the software will help and allow farmers to make a decision in real-time which will lead to saving time, money, and even maybe a crop from the destructive impact of pest or extreme weather.

Replace chemical fertilizer– Chemical fertilizers have an obnoxious effect on the environment.

Organic farming- Usage of natural fertilizer and manure to improve the quality of food. New emerging technologies have shown positive impacts on agriculture. In most countries, agricultural researches and pieces of training, are offered by both government and private sectors. India is one of the leading countries across the globe.

 The agricultural education system in the country offers various degree programs such as Agriculture, Veterinary science, agricultural engineering, horticulture, fisheries, food science, and many more. Agriculturalists are the backbone of the country, without them country is unable to provide good quality food to individuals. Not only this but its also the fact that we won’t be unable to wear clothes. The business and job market has been improved every day with increasing demand in the food industry.

 

Some career opportunities are

  1. Environmental Engineer
  2. bioinformatician
  3. Agriculture teacher
  4. Food scientist
  5. Biophysicist or Biochemist
  6. Agricultural Engineer
  7. Veterinarian
  8. Plant Molecular biologist
  9. Genetic researcher
  10. Crop production analyst
  11. Agricultural Biotechnologist etc.

Reasons to study Agriculture:

            Within another three decades, the population of the Earth is likely to be increased many times than today, and to provide good quality nutritious food available to individuals all of the countries will have to be dependent on agricultural products to fulfill the need for food. New agriculture reforms a technology that will indeed help a large section of people with new job opportunities and livelihood. The raw material produced from agriculture and improvement in agribusiness will further help in the development of the industrial sector.

Impacts of COVID 19 on agriculture across the globe

            As the pandemic COVID 19 unfolds, every country is facing various kinds of challenges. As per statistical data, before COVID 19 pandemic struck, 800 million people worldwide were suffering from chronic undernourishment. The developing countries and the countries facing pervasive poverty and lack of health care systems have been intensely affected. Food security has become a fight across the globe. The international communities and governments throughout the world have emphasized food and food-based safety. With improved technological advancements, a high yield of crops can be cultivated and harvested economically. Farmers and consumers will enjoy the benefits of these technological developments. Recent improvements in the agricultural field will accelerate the economic prosperity of the country.

PROTEIN COMMUNICATION VIA RNA TRANSLATION IN CORONAVIRUS INFECTED CELLS: ROLE OF ACE-2 PROTEIN and MRNA VACCINES

Student Contributor: Anusuya Patra (B.Sc Biotechnology IV sem)

Coronavirus was recognized in mid-1960 and later known to affect humans and a variety of mammals. Since, 2002 two types of coronavirus infecting animals and give risen into humans: Severe Acute Respiratory Syndrome (SARS-CoV) recognized in South China in 2003, & Middle East Respiratory Syndrome (MERS-CoV) identified in Saudi Arabia in 2012. 

The Novel Coronavirus has been identified as Severe Acute Respiratory Syndrome-2 (SARS-CoV-2) identified in Wuhan & responsible for Pneumonia outbreak throughout the world. This outbreak was started in China in 2019; during December & became worldwide in a timeframe of a few months. World Health Organization recognized it as a pandemic on 11th March 2020. So far, more than 200, countries that resulted in above 160,000 deaths as of 19th April 2020. This highly infectious virus spread via respiratory droplets and aerosols when an uninfected person comes with contact with an infected person. Viruses play a crucial role in Covid19 though it’s important to understand the mechanisms of viral mRNA translation via Protein Synthesis. 

PROTEIN STRUCTURE: SCARs-CoV-2 has spherical particles and has proteins called spikes. The viruses are to blame morvic envelope particle (virion) & the RNA in this virus has a single-stranded, positive sense. These viruses are the largest members of the RNA virus with a diameter of around 80-160 nanometer in diameter and genomes range from 21-34 kbs. Coronavirus consists of 5 structural proteins.

  1. S (spike)
  2. N (nucleocapsid)
  3. E (envelop)
  4. M(membrane)
  5. HE (Hemagglutinin Esterase).

The most important and specific proteins are Spike Protein (S) & Hemagglutinin Esterase Protein (HE) and they have covered the outer side of the virus. Both are significantly responsible for attaching, infusing, infecting the particular cells of the body. 

S protein binds with HE protein assists in viral entry to the human cells, and this protein attaches to the receptor protein ACE2, this gives a crown-like appearance, and comes up with a name “Corona”. N protein is a ribonucleoprotein that forms the complex with ribonucleic acid to assists the viral assembly. E protein forms the viral envelope. There are two types of “E protein.” 

E1: is a type of glycoprotein transmembrane protein matrix. 

E2: is a protein that helps in the fusion in human cells. M protein: protein forms a viral envelope. HE protein is a peplomer which has a role in hemagglutination. Communication between viruses and infected lung cells: Once, the virus gets into the respiratory system it loves to attack alveoli. In alveoli, there are two types of pneumocytes. Type 1 pneumocytes: is for gastric exchange.  

Type 2 pneumocytes: culture and expressed the surfactant protein (SP-A, SP-B, & pro-sp-C) at mRNA and protein level it decreases the surfactants in alveoli and collapsed in pressure. S protein binds to a specific receptor on Type 2 pneumocytes, this receptor is known as Angiotensin-converting enzyme-2 (ACE-2). When RNA virus enters into the cell binds enlarge the virus action and engulf the virus taken into the cell, then positive sense RNA comes inside the cytoplasm if the Type 2 pneumocytes, it produces host cell ribosomes and it comes to known as mRNA through the translation process. 

In general virus protein has two receptor binding domain ORBDs, facing downward, and another one facing upwards. These receptor binding domains help viruses to bind and invade human cells. The virus targets human ACE-2 receptor binds with amino acid transporter. The rearrangement of spike proteins that cover the viral surface helps to penetrate the virus cells & these viruses dissolve in the own protein shell & RNA releases bellowed inside the cell. 

Coronavirus hijacks the structure of the cell to reproduce the RNA of the virus takes help the host cells an endoplasmic reticulum (ER) in replicating self and magnification the protein part to make a new virus. Once the hijacked cells go to the Golgi bodies the viral RNA & the proteins in a viral protein shell start packaging.

Cell death is a result when the infection function homeostasis. Single-stranded RNA enhances the production of another enzyme called RNA dependent RNA polymerase; it takes RNA and synthesized RNA and coverts into more copies of single-stranded RNA. There are different types of specific polyproteins also included in the virus cells. 

To make the whole virus structure (like nucleocapsid, specific enzymes, spike proteins), there is a specific enzyme that proteolyzes these polyproteins to individual points to need to make a whole virus structure. So, we have enzymes here specific type of proteinases proteolytically cleave this polyprotein into the different viral components that involved for making into the nucleocapsid, specific enzymes, and spike proteins. 

The cells use RNA dependent RNA polymerase and ribosomes to make a protein, to make the components of the viral protein structure. If we combined all nucleocapsid enzyme spike proteins with single-stranded RNA, it comes out with a whole structure virus. Significance of ACE-2 Protein: Angiotensin released from the liver and this is converted into Angiotensin 1 when it comes to the bloodstream, it gets the lungs to release something known as ACE (Angiotensin Converting Enzyme) this allows the conversion of ACE-1 to ACE-2. 

ACE-2 stimulates sympathetic activity and also stimulates Na2+/Cl- re-absorption and K+ excretion & H2O retention virus from ACE which converts into ACE-2. And in hypertension ACE inhibitors are the first-line drugs. In SCARS-CoV-2 ACE-2 (Angiotensin-converting enzyme 2) is a door from where the cells enter the human body and ACE2 protein have important enzymatic functions influencing blood pressure to the organ. The spike protein interacts with the ACE2 receptor and gets entered into the interior of the human cell and the virus can replicate. Simultaneously the spike protein undergoes in the process of unfolding or refolding. This transformation occurs via coiled-spring that start buried at the core of the spike & the spike hooks reconfigured into the cell and helps to crash virus particles. In this way, the viral genetic material can mediate its way into the unsuspecting cell.

If ACE-2 is decreased then the lungs will be more prone to many viral injuries because the ACE-2 protects the lungs. If ACE-2 inhibitor is activated then there will be more number of dying people from heart failure and the chances of death become two-three folds. Though the tough point is that the ACE-2 protein is very controversial but inhibition of the progression of ACE-1 might be helpful to decrease the level of COVID 19. 

Prevention via ACE-2 and some mRNA vaccines: Human recombinant soluble ACE-2 drug is newly synthesized for the treatment of coronavirus, this drug decodes receptor and connects with the spike proteins envelop of the virus to prevent it from connecting and entering in human cells. Another vaccine is known as the mRNA1273 vaccine stabilizes the mRNA and also encodes for a stable form of SARS-CoV-2 spike proteins. mRNA’s vaccines carry the molecular instruction to make protein. The host body uses to produce viral protein provided via the mRNA vaccine, the mRNA vaccine comes out from synthetic mRNA of the virus & the mRNA vaccines mimic as the natural infection of the virus. 

Advantages of mRNA vaccine: The significant advantage of mRNA vaccines that they can produce pure viral proteins & sometimes saving months or years to standardize and ramp up mass production. 

References:

  • Sarah A. Kopecky-Bromberg, Luis Martinez-Sobrido, and Peter Palese, “7a Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cellular Protein Synthesis and Activates p38 Mitogen-Activated Protein Kinase”, J Virol. 2006 Jan; 80(2): 785–793.
  • The Conversation “What the coronavirus does make to your body that makes it so deadly” National Institute of Allergy and Infectious Diseases, NIH Benjamin Neuman Texas A&M University. Published by April 2 2020.
  • Sanjay Mishra, Robert Carnahan, Coronavirus: A new type of vaccine using RNA could heplp defeat Covid 19 NIAID-RML Vanderbilt University Published by March 26.
  • Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020 Feb 15,395(10223):497-506.
  • Peter & Jack, Coronavirus-Covid 19 | Viral Structure and Pathogenesis Anatomy Zone Published April 3 2020. 

A SCIENTIFIC INSIGHT TO THE ROLE OF ANTIVIRAL DRUG “HYDROXYCHLOROQUINE” AGAINST COVID-19

Student contributors: Rituja Mahalanobish and Ankita Dev (B. Tech Biotechnology)

Hydroxychloroquine is an antimalarial drug that inhibits microorganisms, cellular replication. In recent time COVID 19 is life-threatening disease create pandemic problem in the whole world. Hydroxychloroquine/chloroquine is currently being studied for the treatment and prevention of SARS COVID 2. Mechanism of Hydroxychloroquine and chloroquine both are the same only differ an extra hydroxyl group present in hydroxychloroquine. But the treatment of Covid-19, hydroxychloroquine is more-safer than chloroquine.

Mechanism
Previous experimental studies had demonstrated that hydroxychloroquine /chloroquine has efficient to fight against SARS COVID 1 in vitro. It inhibits or blocks the glycosylation receptor of the cell surface, so the virus cannot bind to the Angiotensin-Converting Enzyme (ACE) 2 which expresses in lungs, heart, kidney intestine. Hydroxychloroquine/chloroquine can interfere with the SARS COVID 2 binding with the ACE 2 receptor.Hydroxychloroquine/chloroquine stops the biosynthesis of sialic acid by inhibiting the quinine reductase 2. Sialic acid is monosaccharides of cell transmembrane which help to ligand recognition. So, SARS COVID 2 cannot bind with the receptors by inhibiting sialic acid biosynthesis. This drug stops the transport and post transport system of Coronavirus. Hydroxychloroquine through inhibition of map kinase interferes with SARS COVID 2 crosstalk. Hydroxychloroquine/chloroquine inhibits the endocytosis. These drugs both can change pH in intracellular organelles. It can decrease the acidic medium in the endosome and lysosome by the increasing pH level. Any type of virus can be rapidly activated in an acidic medium. Hydroxychloroquine drug stops the fusion between lysosome and endosome and makes them dysfunctional. Spike protein is not cleaved by inhibiting cell fusion mechanism. Hydroxychloroquine has an anti-cancer effect and it works as an antiviral agent. It helps to the influx of Zinc into the cells. Hydroxychloroquine/chloroquine mediated Zinc transport into the cell help to increase the amount of zinc into the cytosol. Zinc inhibits RNA dependent RNA polymerase or RDRP enzyme mechanism. RDRP enzyme helps to make viral RNA and help to replicate the virus. Hydroxychloroquine has immune modulators. It prevents autoimmune disorder by suppressing the autoimmune response. It works as an interferon blocker reducing the immune system response to a viral infection. It also inhibits the synthesis of inflammatory cytokines to prevent cytokine storm. Hydroxychloroquine is less penetrable to the blood retinal barrier because it has an extra hydroxyl group. The retinal toxicity is less compared to chloroquine. Hydroxychloroquine is a derivative of chloroquine which is less toxic.

Present researches and scenario of Hydroxychloroquine:

Several studies conducted by researchers have shown that hydroxychloroquine, an antimalarial drug found to be more effective than the standard treatment. Drug research conducted on 30 Covid-19 patients, shows 13 patients tested negative on whom tested compared to 14 patients who were not on this drug though one patient develops a serious illness. Whereas the median time taken for the individuals to recover was similar in both groups. However, according to Thailand Medical News warned all concern not to acquire any experimental drugs or TCM (Traditional Chinese Medicine) herbs and use them by themselves. Researchers recommended taking suggestions from an authorized doctor otherwise it could result in complex medical conditions and life-threatening risk. A study published by French medical journal provides new confirmation that hydroxychloroquine does not appear to help the immune system, clear the coronavirus from the body. Studies found that a combination of Hydroxychloroquine and Azithromycin benefits patients who do not have severe symptoms of this virus.

However, Hydroxychloroquine has also been treated with other drugs such as Azithromycin+ Hydroxychloroquine, Chloroquine+ Hydroxychloroquine. Also remarkably, it can have dangerous side effects, as well as giving people illusions about the drug, because the drug is still under research for treatment of Covid-19 patients. Side effects of Hydroxychloroquine:

The common side effects of hydroxychloroquine:
1. Headache, dizziness, ringing in ears
2. Nausea, vomiting, stomach pain
3. Loss of appetite, weight loss
4. Mood changes, feeling nervous or irritable
5. Skin rash or itching
6. Hair loss As per recent reports by the FDA (Food & Drug Administration), warned the providers that Covid-19 patients could experience life-threatening side effects while taking chloroquine & hydroxychloroquine. It says the side effects include abnormal heart rhythms.

FDA has reported that chloroquine & hydroxychloroquine has negative side effects, used for Covid-19 patients. The drug has not been proven to successfully treat Covid-19 in large medical experiments. Further, researchers have expressed their concern about acclaiming the drug as a potential treatment for Covid-19. Patients with heart problems & other fundamental medical conditions have a high risk of undergoing negative side effects from hydroxychloroquine.

REFERENCES:

• Hydroxychloroquine: Can the anti-malarial drug contain COVID-19? Published by The Hindu Net Desk CHENNAI, APRIL 08, 2020

• Awadhesh Kumar Singh, Akriti Singh, Altamash Shaikh, Ritu Singh, and Anoop Misra Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries, Diabetes Metab Syndr. 2020 May-June; 14(3): 241–246.

• Liu, J., Cao, R., Xu, M. et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov 6, 16 (2020).

Strategic Pathways towards COVID-19 diagnosis & treatment

Student contributors – Rahul Dutta, Shaurav Bhattacharyya, Aniket Das ( 3rd year B. Tech Biotechnology)

            The World is witnessing an era where the tiniest being, a mere virus, has taken control over the so-called intelligent minds. Is this the curse of the Almighty or the action of the Evil is not known but what is known is that we must win over this battle to save the innocent human hearts who are becoming victims in the hands of this deadly virus. In recent years, the world is seeing a surge in large-scale epidemics from emerging viruses (like MERS, Ebola & the present SARS-CoV-2) and it is seen that the initial zoonotic animal-to-human transmission event is involved significantly in all of these epidemics. Each time, the viral threat is glorified by the lack of rapid diagnostic testing and quick treatments to obstruct the spread thus hindering public health. The scientists and researchers at every corner of the globe are working relentlessly to find a solution at least to curtail the steep progressive curve of the no. of deaths until the proper vaccine is successfully developed. Here, we are presenting some of the directions in which the scientists are trying to find a way to combat the present crisis scenario.

Utility of BCG Vaccination:

            Scientists have found that heterologous protection conferred by the BCG vaccine could also be effective in patients who have contracted the COVID-19 infection. This is evident from the fact that higher mortality rates are observed in those regions not having universal BCG vaccination policies like Italy, the USA, etc. The protection that the BCG vaccine is conferring can be due to its non-specific mode of action. This means that molecular similarity between BCG and other viral antigens could have led to the formation of some memory B and T cells which can recognize both BCG and other respiratory pathogens. It has been also investigated that BCG could have stimulated the epigenetic reprogramming of the innate immune cells. The monocytes may have undergone modification at the promoter sites of the genes encoding inflammatory cytokines which are now resulting in a more active immune response as those modified monocytes have been reactivated & triggered by the coronavirus antigen in those who have received the BCG vaccination previously.

Applicability & future of Nanotechnology:

            Today nanotechnology or the science of nanoscale structures is one of the most interesting branches of science. A new nanomedicine developed at the SN Bose National Centre for Basic Sciences (SNBNCBS) in Kolkata, has the potential in the treatment of Covid-19. Our body continuously adds and removes oxygen through oxidation and reduction (redox) reactions. However, reactive oxygen species (ROS) free radicals are also generated from these processes. During the viral or bacterial attack, ROS, or oxygen stress level of our body is naturally generated by our immune cells so that they can efficiently perform their functions. In the new nanomedicine formulation, nanoparticles extracted from manganese salt are combined with the citrus extract. Clinical trials on mice have shown that the new nanomedicine adds up the oxidative stress in a controlled manner and thus finds a potential application in controlling virus infections like the Covid-19. Another interesting application of nanomedicine is the use of silver nanoparticles. Colloidal silver or a suspension of microscopic, electrically charged particles of silver bear a wide potential to act against almost 650 different kinds of pathogens which include bacteria, fungus, and viruses. They aid in inhibiting the oxygen metabolizing enzymes in these pathogens. Covid-19 infections start mildly in the upper respiratory airways. Hence it can be applied through inhalation delivery methods to suppress the proliferation of the virus during the early days of infection.

Remarkable potential of CRISPR-based diagnostics & therapeutics:

            CRISPR (clustered regularly interspaced short palindromic repeats) is referred to as a family of DNA sequences that are exclusively found within the genetic makeup of prokaryotic organisms. These sequences are derived from DNA fragments of some previously attacking bacteriophages. The CRISPR sequences whenever they encounters any complementary DNA sequence concerning it, they bind to that and the Cas9 (CRISPR-associated protein 9) nuclease-type enzyme associates with the CRISPR sequences & cleaves those specific strands of DNA. Thus, whenever, any future invasion of the same bacteriophage occurs, this phenomenon inactivates the invading DNA of the attacking bacteriophage thus conferring the prokaryotes with a mode of acquired immunity. This technique can be harnessed and applied in viral and pathogen rapid diagnostic and therapeutic purposes. Cas13 nuclease-type enzymes are RNA-targeting proteins by virtue of which property, these nucleases can degrade specific target RNAs without producing any effect to the host genome. This property makes Cas13 nucleases an interesting candidate for study. On the other hand, Cas12 type nucleases work on DNA. Both Cas12 and Cas13 nucleases can also cleave other nucleic acid molecules (except the target ones) present in the vicinity of their target site. This trait (called the trans or collateral cutting activity) can be applied to CRISPR diagnostics where the non-targeted nucleic acids can be utilized to make certain color-tagged probes for detection purposes.

            Feng Zhang’s group first reported a CRISPR-based nucleic acid detection technique called SHERLOCK (Specific High sensitivity Enzymatic Reporter unLOCKing). Zhang and his team identified two genes (S gene and Orf1ab) from the SARS-CoV-2 genome as their targets. In the SHERLOCK protocol for coronavirus detection, firstly, the synthetic viral RNA is amplified by applying the recombinase polymerase amplification (RPA) technology. This process is followed by in vitro transcription where the amplified DNA gets converted to RNA. Then, RNA detection is done using Cas13 nuclease and specific crRNA (gRNA) targeting specific sequences. Finally, the visual color readout is done where the cleaved reporter RNA with labeled ends are captured on specific antibody bands (to form the visual test band) on lateral flow strips. This protocol has been demonstrated to detect coronavirus RNA from patient samples in very less time (almost less than an hour) and here no special instrumentation is required (as isothermal signal amplification process proceeds through a constant temperature thus not requiring the thermocycler as required by the qRT-PCR technique).

            Mammoth Biosciences proposed a new method which is DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR) assay which recruits Cas12a for sensitive DNA detection purposes. The method utilizes the same CRISPR-based detection of the two genes (N-gene and E-gene) which, by bioinformatics computational methods, are found to be conserved in SARS-CoV-2 genome. This method utilized the technique of Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) for amplifying the RNA strands to generate a huge number of DNA strand loops and this method takes about 30 minutes which is less when compared to the SHERLOCK-based protocol. This is because here, no extra time is required to be spent on the additional IVT steps. Such a rapid diagnostic platform would be particularly valuable in high-risk areas such as airports, clinics, and hospitals. 

            Other than detecting, a new CRISPR-based antiviral strategy targeting the SARS-CoV-2 virus appears to effectively degrade RNA (as has been proposed in a Stanford paper). This aids in killing or knocking out the virus which can thus be subsequently applied to the therapeutic sector. This approach, termed PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells), employs six CRISPR RNAs that can target 91 percent of the 3,051 sequenced coronaviruses, thus signifying its broad coverage. This CRISPR-based approach recruits Cas13d type RNA endonuclease which employs customizable CRISPR-associated RNAs. The reason for choosing Cas13d over other Cas13 proteins is because it has a small size, is highly specific in action, and possesses a strong catalytic activity. Cas13d is made to target & destroy two conserved sites of the SARS-CoV-2 viral genome, which encode the RdRP and Nucleocapsid proteins, known to be essential for coronavirus replication and function. This technique now needs to be tested & validated with live SARS-CoV-2 viruses and whether they are having any off-target side effects must be thoroughly evaluated via clinical screening. An effective and safe in vivo delivery method into the human respiratory tract cells must be developed. The remarkably great potential of the CRISPR-based therapeutic systems lies in the fact that once the genetic targets of a new virus are identified, altering a previous treatment becomes simple which can be quickly implemented during the birth of any future pandemics.

Conclusion:

Hence, it can be inferred from the above discussion that the BCG vaccination strategy, the application of nanomedicines, and the CRISPR-based diagnostic & therapeutic systems hold a great promise & a bright future to emerge out victoriously against the threat of Covid-19.

References

 

Let’s talk about the importance of Plant and Agricultural Biotechnology: A lot more than just GM crops

Student contributors: Rudranil Samanta and Rumale Das (B.Tech, Biotechnology)

Nature is an artist which keeps on blissfully making new creatures with different size and shapes using different colors and qualities. On this planet, life exists in the form of 8.7 million species that live together under the guardianship of nature. All living beings are blessed to opt for the changes within themselves to survive in the available niche not only this but according to the environments, living objects undo the process of adaptation to compete and survive in a better possible way. So among all the existing creatures on the Earth, here is a discussion based on the plant system to explain the importance of plant and agricultural biotechnology in this modern world. The best possible character of a plant is supposed to be a good productive nutritious crop, high-quality yield capacity, disease resistance, stress tolerance power, and many more depending on what type of plant we are looking for. All plants will try to develop these characteristics within themselves for a better survival but this adaptation may take hundreds of years to fulfill the demand of the world. This is not a new phenomenon as we all are aware of the natural selection theory of Darwin. According to Darwin [he had] called this principle, by which each slight variation, if useful, is preserved, by the term of Natural Selection (Charles Darwin). Now the role of biotechnology comes. Before starting the discussing let’s first understand what biotechnology is? 

8.7 Million Species

Biotechnology is defined as a set of tools that uses living organisms (or parts of organisms) to make or modify a product, improve plants, trees or animals, or develop microorganisms for specific uses. And when this is focused on plant and agriculture system then it is termed as “Plant and Agricultural Biotechnology” which is used for crop improvement through biotechnology tools. This area of science and technology is introduced to students of Adamas University with the subject names as Plant & Forest Biotechnology (SBT43104) as well as Plant & Agricultural Biotechnology (SBT52101) during their B. Tech and M. Sc courses respectively, offered by Department of Biotechnology under the School of Life Sciences and Biotechnology. Our students learn that this subject deals with a specific area of Biotechnology incorporated with plant sciences and they also learn about the use of scientific tools and techniques including genetic engineering, molecular markers, molecular diagnosis vaccines and tissue culture to modify living organisms- like plants, microorganisms, animals. They also understand that we can also treat environmental problems with the help of plant systems and biotechnology.

Let’s talk about the need and importance of this field and let’s expand our knowledge in this direction to gain a better understanding that this area of science and technology is not all about genetically modified crops but it’s a lot more than that, what our students learn in our Adamas University.

Plant and Agricultural Biotechnology is the majority important to alter the genome sequence of crops and those crops can be termed as transgenic and genetically modified crops with good productivity and good food quality. Yes, these crops are called GM crops. Being a developing country, we know India is based and specifically known for its agriculture throughout the world, farmers are like God to us but these farmers face several challenges just to make good yield with high quality, which we may not be aware of. But actually, many Biotic and Abiotic factors are challenging our agriculture systems. Plant and Agriculture Biotechnology helps to face and overcome these problems so that good quality food can be available not only for our Nation but for the entire world. This is not a single field, it is a combination of different scientific fields of Agriculture like Plant Breeding, Plant Pathology, Agronomy, Entomology, horticulture, vegetable sciences with a combination of the biotechnological field including Genomics, Proteomics, Genetic Engineering, Bioprocess Engineering, Immunology, molecular biology, and microbial technology. Not only this but here we learn about statistical technologies as well as advanced computation technology with system biology. Hence it is such a vast field and we try to introduce our students what is the need of today especially in the Agriculture and how they can draw their future in this area as a Professor, an Agricultural Scientist, a Plant Biotechnologist, a Genetic Engineer and they can also be a Career Counsellor of this field.

However, Plant and Agricultural biotechnology offer a great platform in agriculture but this field is not limited to just agriculture only, it has a great scope in medical and pharmaceutical science as well. We can understand this by going through some current researches where Plant and Agricultural Biotechnology was used for vaccine production against coronavirus. Researchers in Spain used Plant Biotechnology to produce SARS-CoV-2 vaccines as per the report by International Service for the Acquisition of Agri-biotech Applications (ISAAA) published by 15th April 2020. They used a plant system “Nicotiana benthamiana” as a biofactory of thye vaccines, not only this but according to research, Queensland University of Technology successfully sequenced the Tobacco genome and now it is also used to develop a vaccine against COVID-19 reported by 8th April 2020. A month back by March 18, 2020, Canadian biopharmaceutical company “Medicago” got reported to develop viable vaccines candidate for COVID-19 and they also used the properties of Plant-based technology.

So, it is a field full of challenges and excitement for the students. Our students not only learn the concepts but they enjoy different experiences in this field. We provide well-equipped laboratories having sophisticated instruments and hand-on practice for the students so that the concept and the principle of all techniques will not be limited to the theoretical knowledge only but they will be able to gain practical knowledge as well.

With the concluding note, we would say that Sir Mankombu Sambasivan Swaminathan had given a great contribution to our Nation with the dream to fight against hunger. Somewhere he could fulfill the dream but with a high rate of increasing population, good quality nutritious food is the requirement of today’s world. This field of science and technology can help us to build a better nation. You can be the next to help our Nation to fight against hunger and to develop such a technology that will be able to provide good quality nutritious food to everyone in an affordable way. Let’s dream together and work together to build a healthier nation.

Flatten the Curve, Raise the Line and Beat the Corona virus

SARS- CoV 2 corona virus is now the cause of an outbreak throughout the world with the name of “COVID 19”. This corona virus has led to a pandemic that threatens everyone therefore the basic concept and knowledge about this pandemic situation is known to all of us. But how to treat the situation, what are the strategies applied in this direction, what are the possible ways to overcome this problem, these are some ongoing thoughts of everyone’s mind. So here is a good news that Yes! We can fight the pandemic. If we follow some strategies, we all can fight and win over this situation. Most importantly, this time is not to be panic but it’s the time to unite together against the pandemic. Before understanding the strategies we must know about the epidemic curve.

 

Epidemic curve: In case of pandemic, every single individual is on a great risk to get infected and a number of new outbreak cases are being reported with every passing day. So the epidemic curve represents the new outbreak cases by the day of onset of the disease to understand the present condition. The overall shape of this curve helps us to observe the current situation and to understand the type of outbreak we’re dealing with. The X-axis of this curve represents ‘the time (date)’ whereas the Y-axis represents the number of new outbreak cases. There is also a horizontal line parallel to X- axis which represents the capacity of the community health care system that means the hospital capacity including beds numbers, available staff and other important measures available for patient care.   So in general condition the curve should not go beyond the threshold line (fig a).

 

But what happens when it comes to a pandemic? A pandemic results a sudden rise in the number of patients. Today, many countries have met this critical situation when the community health care systems are leading to less availability of resources for a proper treatment of all types of patients at the same time as they are already operating close to the capacity line. We can visualize the progress of a disease outbreak over time by observing the changes in the shape of epidemic curve. Whenever a pandemic occurs, it is believed that the infectious agent spreads very rapidly and the curve can rise and cross the line. In this critical situation, the healthcare system can no longer meet the needs of COVID-19 patients as well as all the other types of patients and at this point the mortality rate starts to rise quickly as people are unable to get the best care and outcomes. For these reasons, health care systems have to fellow two strategies to save a large number of lives. These strategies are as follows:

Strategy 1: Flatten the Epidemic Curve

To achieve the first strategy the rate of infection should get slower and in this case the epidemic curve will be observed flatter than the normal situation (fig b) and this is called flattening the epidemic curve. It does not mean the infection will not spread among but a flatter curve assumes the same number of people will get infected over a longer period of time so their

Key factors to flatten the curve:

a). Social distancing: Now a key factor to flatten the curve is social distancing, which refers to measures aimed at reducing close contact between people. This is why governments are closing schools, non-critical businesses and other places where people gather like sporting and social events. By limiting interactions between individuals, we can limit the spread of the disease. This is why it’s so important to educate as many people in the community as possible through online education, news articles and even social media posts.

b). Practicing good hygiene: Apart from social distancing, there are a number of key behaviours that you can do to help, like practicing good hygiene by washing your hands frequently and cleaning frequently touched objects and surfaces.

c). Isolating in confirmed and suspected cases: as well as isolating in confirmed and suspected cases.

While Health Care Systems are doing their part to help flatten the curve, they also need to meet the increasing demand. This is raising the line of our health care capacity.

Strategy 2: Raise the line

The strategy 2 is all about to increase the capacity line of health care systems in term of hospital beds, staffing, available equipments and all possible care which should be provided to the patient. As the demand is increasing day by day, many countries are unable to provide all facilities to patient suffering from Covid-19 as well as other diseases. Now the question is how to increase the capacity of heath care systems? Yes, the infection is spreading with a great rate and the suspected patient visiting to hospitals may be a carrier of corona virus and can be infectious to other patient present in hospitals as well as for health care providers.to avoid these problems and to increase the capacity there are some important steps taken by health care people:

 

  • Discharging healthy patients from hospitals as quickly as possible
  • Cancelling elective procedures and ramp up staffing
  • Health care providers are arranging acute facilities to deal with the waves of corona patients.
  • The supplies of protective equipment should remain adequate throughout the pandemic.
  • Health care providers should figure out ways to provide online health education opportunities.
  • Health care providers should see patients with home care and telemedicine.
  • Hospitals should make every effort to keep corona patients separate from non corona patients to reduce the chances of intra-hospital spread. 
  • Not only patients but health care providers should also get proper care and personal protective equipment like N95 masks.
  • Ultimately the curve should be kept below the capacity threshold to ensure the resources will be equally available for patients.

These two strategies are proving themselves as the best option during the rising magnitude of corona infection. Few points to remember always are:

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