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Author: Rudra Prasad Saha

#BiotechnologyNext : The COVID-19 pandemic: present status and future opportunities for students

In the current pandemic COVID-19, the importance of civic responsibilities is immense to curb the spread of the infection. Unfortunately, it appears that at least in India the lack of civic responsibility is one of the reasons for the recent spike in the number of infections. As of 5th August 2020, the total number of coronavirus cases in India has crossed 1.9 million with over 39,000 deaths (2.1% mortality rate), whereas worldwide total infected cases are over 18.8 million with more than 700,000 deaths (3.8% mortality rate). Initially, India has managed to curtail the spread of the virus mainly due to its timely strict lockdown and social distancing regulations, but the recent relaxation on the lockdown appears to increase the total number of infections. 

India is known for its rich diversity where various religions coexist in harmony, but sometimes diversity, religious beliefs create roadblocks especially what we have seen during the lockdown period in India. It was not an easy task to enforce social distancing norms where social mixing is what loved by most of the 135 billion people in India. Despite all the hurdles India appears to curtail the spread of the virus significantly compared to several developed nations in the world. India fared much better, in terms of mortality rate, compared to the nations with highest numbers of COVID-19 deaths like USA (3.3% mortality rate), Brazil (3.4% mortality rate), UK (15.1% mortality rate), Mexico (10.9% mortality rate), Italy (14.1% mortality rate), France (15.6% mortality rate), and Spain (8.1% mortality rate). Although these numbers are dependent on how many testing is done in each country, at this point most of the countries have increased their capacities significantly; for example, India is currently testing more than 0.4 million per day and increasing its capacity to test 1 million samples a day. 

Despite apparent better management and low mortality rates compared to most of the other nations, the medical treatment offered by the healthcare professionals in India needs serious rethinking. The Indian Council of Medical Research (ICMR) under the supervision of the central government has recommended hydroxychloroquine (HCQ) for prophylaxis to healthcare workers treating COVID-19 patients and asymptomatic persons who have been in contact with a positive patient. In some cases, HCQ was found to be administered along with azithromycin to ailing COVID-19 patients. The hype around the HCQ, coined as ‘wonder-drug’, fizzles out recently when reports have started to show that HCQ does not affect the COVID-19 patients. No other country in the world has recommended HCQ as a prophylactic. The use of HCQ, therefore, has to be regulated as it may cause serious damages to the COVID-19 patients if taken unsupervised by the doctors. HCQ is cheap and readily available in the Indian market and that prompts the general population to embrace it as the cure for COVID-19. Although there are some positive effects of HCQ found in some COVID-19 patients, the use of the drug without the recommendation of doctors should be strictly controlled.

Unfortunately, in India, not too many alternatives are available to HCQ for treating COVID-19 patients. The drug remdesivir which has shown some benefits to COVID-19 patients is available in India but too expensive for most of the patients. Another alternative Indian government looking at is convalescent plasma therapy where recovered patients plasma with antibodies against coronavirus is used to treat new patients, but again for a pandemic like COVID-19 plasma therapy has its limitations. Another immunosuppressive drug tocilizumab is being used in some critical patients having signs of ‘cytokine storm’ which can destroy a patient’s lung and cause multi-organ failure. Unfortunately, the drug is costly and requires monitoring of the patient’s IL-6 levels which again is a costly affair in India. Until the discovery of potent drugs or vaccines to treat COVID-19 supportive treatment is the only option, but the use of HCQ requires extreme caution especially in India. Therefore, strict social or physical distancing norms and other safety measures are only remedies available for the general population to stop the spread of the virus, but the recent relaxation of the lockdown in India and the spike in the number of infections proves that we need to be very careful about the physical distancing and should maintain civic responsibilities strictly if there is any hope to curb the spread of COVID-19 in absence of any potent drug or vaccine for the foreseeable future.

At present 37 coronavirus candidate vaccines are under various phases of clinical trials (source: https://www.bioworld.com/COVID19products), and three of them are at the final phase III trials. Several Indian companies/organizations are also developing coronavirus vaccines, e.g., Serum Institute of India, Bharat Biotech, Zydus Cadila, etc. Therefore, the opportunities in the field of vaccine development and allied fields have increased multifold in recent times. Students from various biology fields, e.g., Biotechnology, Microbiology, and Biochemistry, are in demand. Even in the post-COVID-19 era, the demand for the students from Biotechnology, Microbiology, and Biochemistry streams are going to increase as there will be a stronger focus on health henceforward. SARS-CoV-2 is not the last virus discovered that can infect humans as many more are predicted to be discovered in the future. Therefore, government and non-government funding are expected to increase in understanding these pathogens and how to develop drugs or vaccines against them in the future. Students who know about Molecular Biology, Genetics, Bioinformatics, Genetic Engineering, Immunology, Virology, etc. are going to be in demand at present and the future.

The impact of Bioinformatics in the development of vaccines against COVID-19

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent for the Coronavirus Disease 2019 (COVID-19). Since its first detection in December 2019 the disease has engulfed almost entire world by spreading over 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 in contact with an infected one. Without any drug or vaccine at sight, the world is slowly succumbing to the disease. Therefore, researchers around the world have started collaborating and sharing their research data so that with concerted efforts a cure for the disease can be developed quickly. In this challenging scenario, Bioinformatics came out as one of the essential tools to analyze viral data as it provides vital information about the genetic makeup of the virus and also assists directly in the development of drugs or vaccines against the deadly disease.

Bioinformatics can significantly reduce the cost of research by predicting a few plausible directions amongst hundreds of options. A large amount of data can be analyzed by Bioinformatics to come up with a hypothesis that can be further validated in the laboratory by doing experiments. Instead of doing a bunch of experiments without a clear goal, a few can be tested as predicted by Bioinformatics by analyzing the available data. That way a researcher can save a lot of money and manpower, and also results can be obtained quickly. In the current COVID-19 crisis also Bioinformatics is playing a crucial role by predicting suitable drugs against viral targets and subsequently these are now being tested in the laboratory for validation.

To develop a potent drug against COVID-19 Bioinformatics can help by predicting possible molecules as inhibitors for the virus that can be tested in the laboratory for efficacy. Using certain computational tools or self-written programs a Bioinformatician can predict possible molecules that can be used as drugs against the disease. From analyzing the sequence to the final drug candidate prediction requires several steps to follow which can be broadly divided into five segments – retrieval of the viral sequence from the nucleic acid database, analysis of the sequence data by comparison with other viral sequences, phylogenetic analysis of the viral sequences to find out how the target virus evolved from others, computational modeling of the important viral proteins as drug targets, and finally test several drug molecules against the viral proteins for inhibitory activities.

Bioinformatics Databases:

Immediately after the discovery of the SARS-CoV-2 in Wuhan city of China in December 2019, scientists experimentally determined the sequence of the virus and deposited that in the public database so that others can access it freely and work on it. Bioinformaticians downloaded the sequence from the database and started analyzing the sequence to extract useful information about the virus as this is the first step in the drug development against COVID-19.

Sequence Comparison:

The SARS-CoV-2 sequence was compared with other viruses, especially other coronaviruses, and found that it has sequence similarity with SARS-CoV which was responsible for the previous SARS outbreak in 2003. Also, the SARS-CoV-2 sequence was found very similar to a coronavirus found in bats and from that information it was predicted that the virus was probably originated in bats. Subsequently acquiring favorable mutations or changes in its genome the virus jumped to humans from bats thorough a pangolin intermediate – all this information was obtained by analyzing viral sequences which again indicates the significance of Bioinformatics.

Phylogenetic Analysis:

From sequence and phylogenetic analysis scientists also found out that at least three different strains (types A, B, and C) of the virus are currently circulating in different regions of the world. Type A was the ancestral strain that moved from China to Europe and the other strain B originated from A and then moved to America. Type C again originated from A by changing its genome and currently prevalent in Asia. All these fascinating information was obtained due to the help of Bioinformatic analysis.

Building Structural Models:

Once the genetic information of SARS-CoV-2 was analyzed to find out genes that it holds and what type of proteins it encodes, scientists generated theoretical models of all the important proteins of the virus. If one can inhibit those essential proteins of the virus, the virus can be stopped from further infecting others. In the absence of any experimental structures of the viral proteins, theoretical models can be built by a process called homology modeling where if structures of similar proteins from other viruses are available those can be used as templates to generate theoretical structures of target proteins. Structures of the proteins are important for designing drugs against those, and therefore, scientists built theoretical models of important viral proteins that can be targeted by inhibitor molecules.

Drug Designing:

The final step in the process is to use existing drug molecules or modify the structures of existing drug molecules and ‘dock’ them against the viral proteins to see whether these molecules are binding to the important sites on the viral proteins or not by computational analysis. If some molecules are found which can bind to the viral proteins with high affinity, then those molecules can be further tested in the laboratory to find out their effectiveness. This way Bioinformatics can help immensely to design new drugs against the SARS-CoV-2 and stop COVID-19 from further spreading. Already the scientists have designed several inhibitory molecules against SARS-CoV-2 and now these molecules are being tested experimentally to find out which one is the most potent in COVID-19.

Bioinformatics Scope in India:

The current crisis has shown the importance and reach of Bioinformatics applications, and why it is an essential component for a biologist to know. Unfortunately, in India the Bioinformatics jobs are limited and it is considered as a part of the Biotechnology course. As Biotechnology jobs are available in much higher numbers compared to Bioinformatics jobs in India it is recommended to students that they should pursue Biotechnology careers. Therefore, students who would like to pursue Bioinformatics careers they should either pursue Biotechnology undergraduate programs like Biotechnology BSc or Biotechnology BTech, or pursue postgraduate program like Biotechnology MSc, but make sure that Bioinformatics course is an integral component of any of these programs. At the Adamas University, the School of Life Science & Biotechnology offers BSc, BTech and MSc programs in Biotechnology. All these programs have Bioinformatics as one of the major components for study. We hope the cure for COVID-19 is found soon so that we can get back to our normal lives again, but it is no doubt that Bioinformatics applications would play an important role in finding the vaccine.

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