Breaking Boundaries in Drug Research: Dr. Neeradi Dinesh's Inspiring Path

Dr. Neeradi Dinesh is an accomplished Postdoctoral Research Fellow at the Centre for Cellular and Molecular Biology (CCMB) in Hyderabad, with an extensive background in Pharmaceutical Biotechnology, Molecular Biology, and infectious diseases. His academic journey is marked by significant achievements, including securing an All India Rank 1 in NIPER's entrance exam, underscoring his expertise in the field. Dr. Dinesh completed his Ph.D. in Parasitology and Biotechnology at the National Institute of Pharmaceutical Education and Research (NIPER), where he conducted advanced research under the guidance of Dr. Sushma Singh.

With over eight years of postdoctoral experience, Dr. Dinesh has contributed to research in areas such as pre-clinical toxicity testing and the development of new pharmaceutical formulations. His work at the National Institute of Nutrition (ICMR) involved rigorous testing of various formulations, including vaccines and nutraceuticals, using animal models to understand their safety and efficacy. His contributions continue to make a meaningful impact on the advancement of pharmaceutical research and healthcare innovation.

Pharma Now: Dr. Neeradi Dinesh, welcome to Pharma Now. We are very excited to have you. Just to give our readers a brief introduction of yours: You held the 27th rank in GATE in 2008. You have also achieved the All India Rank in NIPER, and you are the winner of the Young Scientist Award. We are very excited to know more about you. So, for our readers, can you share how your journey started and give us a brief introduction of yourself.

Dr. Neeradi: So, when I was doing my bachelors in pharmacy, someone suggested that I attempt the Graduate Aptitude Test in Engineering (GATE). I was impressed with the stipend, especially. At that time, they used to give Rs. 5,000 per month. So, I started my preparation for GATE and secured a very good rank. Then, after cracking GATE, I applied for the National Institute of Pharmaceutical Education and Research (NIPER), it's the top most institution in India in the pharmaceutical sector. It's a government institution. So, I aimed for NIPER and I secured a very good rank. So, I was able to complete my masters there. At NIPER, I started my research work in different areas like infectious disease, Leishmania, and other research areas. I became curious about research; so, I appeared for the NIPER entrance exam, PhD entrance exam and secured the All India 1st Rank. There, I started my research and career in R&D. 

Pharma Now: You mentioned Leishmania or the Kala-azar disease, can you shed more light on the disease? Can you also share some details of your work related to this disease?

Dr. Neeradi: Kala-azar is also known as Leishmaniasis and is caused by Leishmania parasites. This parasite especially infects people living in slum areas, particularly those that are not hygienic. Five states in India are mostly affected by Kala-azar, that is, Bihar, UP, West Bengal, Punjab and Delhi. These are the 5 worst states affected every year. 10,000 people including adults and children die because of this disease. Among other countries, Canada and China are worse affected after India. We selected this disease during my research work because it has no proper treatment, and no drugs are available for the disease. Only few drugs are available, and they cause more side effects. 

So, we started doing research on Kala-azar to identify new drug targets and new drugs. I worked with various clinical samples. I went to different states like Bihar and UP and saw real examples, real patients including children. They were suffering from this disease. They had inflamed internal organs like liver, kidney and stomach, and very slowly people were dying. So, I collected the clinical samples and we started analysing the main symptoms and targets. We identified a drug target for Leishmaniasis, and at the same time, I screened thousands of samples because at NIPER we have different departments: Chemistry department, Cology department, and Biotechnology department. Working in collaboration with all these departments, I screened thousands of molecules to identify the lead molecule for treatment. 

By the end of my study, I found 6 lead molecules for killing the parasite at a minimal concentration. Next, we filed for patents and got two patents successfully. It is in the process of coming to the market. But once the technology transfers then to MNCs and if they take the initiative, we hope it will come to the market.

Pharma Now: You mentioned earlier this disease was more prominent in the rural areas than urban areas and in places with poor hygiene? Can you please explain how these conditions influence the disease?

Dr. Neeradi: Because we are a developing country and there are few states where the population is very high and no proper hygiene, medication, and vaccination has been done, this kind of disease excels and infects people in large numbers with no proper diagnosis. In poor states, there are no proper diagnoses until the patient becomes very serious. Then, they will go to the hospital and the test is done. Unfortunately, by this time, the disease has already spread all over the body. This is the biggest problem in our country. These types of diseases need proper diagnosis and proper treatment, so we aimed to identify drug targets and drug molecules.

Pharma Now: So, by identifying these, can the disease be treated better? Can you please elaborate more on how Kala-azar spreads and works?

Dr. Neeradi: The problem with Kala-azar is that there are two stages: the first stage is the vector—which is sandfly—and the second stage is humans. The main problem with Kala-azar is that it directly infects macrophages. Macrophages are the main cells in our body. If a foreign particle comes inside the body from the outside, macrophages will engulf monocytes. Then, monocytes will engulf the foreign particle and become macrophages, killing the foreign particle. But in Kala-azar, the monocyte is their home. They are the protectors of our body, but this parasite makes the protector cell its home. So, there is no product against this parasite when it comes inside our body and eats monocytes itself. Hence, we are not able to identify Kala-azar. The truth is that this is why it is spreading fast. Once it infects monocytes, it becomes a macrophage and then resides inside the monocyte and spreads to other cells. So, there is no control over the parasite. For example, TB bacteria enters the body. It will affect our lungs, and our monocytes will go and attack the TB parasite and kill it. But in Leishmaniasis, the monocyte is the home, so there is no other cell to kill. That's why it is very different from other diseases, and it is getting resistance and controlling the body and spreading over the body. This is another difficulty for treatment, including the lack of treatment and drugs. 

Pharma Now: I think I understand how Kala-azar spreads. I think your finding of six targets will definitely help us treat the diseases. You mentioned that you worked at the National Institution of Nutrition (NIN), can you tell us more about it?

Dr. Neeradi: After completing my PhD, I joined the National Institute of Nutrition as a postdoctoral fellow. Then, I got the opportunity to work in the pre-clinical docs college department. One interesting thing I worked on was Maggi, the 2-minute food. At that time, based on the report the government gave us, our project was to identify different chemical levels in Maggi. So, we collected samples from different parts of India and analysed them. We found that the SAB and lead levels were very high in Maggi, which gave it the unique taste. Because the levels were very high, we gave our report to the government and Maggi was banned for almost 2 years.

Pharma Now: Based on my limited knowledge, I think most foods have lead or some other chemicals in them. Is that correct?

Dr. Neeradi: Yes. In processed food materials, manufacturers add lead and other chemicals to get the desired taste. However, they should be at low levels. But, sometimes, maybe knowingly or unknowingly, lead levels become high. Lead is carcinogenic, and that’s why its consumption should be monitored every day. 

Pharma Now: As you have said you have worked with NIN during the Maggi project, can you please elaborate more on that? I think analysis of such a large brand may be complex. How did you undertake this study?

Dr. Neeradi: When I was working in the pre-clinical docs college department, I got an opportunity to work on various projects, and one among them is Maggi. For the Maggi project, we collected samples from different Maggi plants in India, specially central India, north India, south India, east India and west India, we also collected samples from the supermarket and analysed various chemicals like lead and SAB chemicals, which impart the food its taste. Every food has some chemicals, but when we analysed the levels, they were very high. After being banned for 2 years, they appealed to the government and proved that they could maintain proper levels, so they got the approval.

Pharma Now: What challenges did you face during the inspection? Also, What is the process of the testing in such projects?

Dr. Neeradi: As you know Maggi belongs to Nestle, which is the top most company in the world. It was very tough for us because they followed all conditions, but we started analysing Maggi using different methods like different chemical analyses, different microbiology analyses, and pharmacology. With support from all departments, we identified the different chemical levels in the product and finally found that the levels of these two chemicals are very high and very toxic to humans. 

Pharma Now: This is a really interesting project that you have worked on. I understand that you are also a member of the Center of Cellular and Molecular Biology. Can you tell us more about that?

Dr. Neeradi: After my postdoctoral work at the NIN, I started working at the Centre for Cellular & Molecular Biology. It is the very prestigious Institute of India. There I worked on basic science as a biotechnology person. There I got more opportunities and worked on different diseases. I joined the malaria lab. There, I worked on vaccine identification for malaria because it is a very known disease throughout the world that is killing people. So, we started working on vaccine identification for malaria and found a target for vaccine molecules. We worked on an autophagy mechanism. It is a self-killing mechanism that can be applied on parasites.

Pharma Now: Can you please explain what the autophagy mechanism is and how it works?

Dr. Neeradi: Autophagy means self killing. Our body has a mechanism to kill cells. The cells that are not working properly are killed, or those above the age limit are killed. For example, red blood cells (RBCs) will only survive for 120 days. After 120 days, RBCs should be removed from the body. In the same way, every cell has a certain time limit. After that time limit is reached, there are some specific proteins in our body that find aged cells and kill them. This is called Autophagy. If the cell is not properly working, is working abnormally, or has aged, it will be eliminated from the body via this self-killing mechanism—Autophagy mechanism. There are different proteins and different genes working on it, and we identified Autophagy genes to find new vaccine molecules for malaria.

Pharma Now: Our body is very intricately designed and has a lot of natural processes to generate new cells and remove dead cells. I think it’s very innovative that you used this existing technology to find a vaccine for malaria. I think all of your team was working on infectious diseases, so how did this shift during COVID? Can you tell us how you contributed to the COVID vaccine?

Dr. Neeradi: When I was working on the malaria vaccine at the Center of Cellular and Molecular Biology at the infectious disease department, we had three labs. We worked especially in the malaria lab, the TB lab, then the hepatitis virus. But in 2020, the COVID pandemic happened all over the world, especially in India and Telangana. When COVID happened, all of our work shifted to COVID because we have to deal with pathogenic parasites like malaria and TB every day so we know how to handle them, but COVID was different. So, according to the Government's proposal, as an emergency, we stopped all our work and started working on COVID diagnosis.

In 2020, we were the only people working for the Telangana government to diagnose the initial stages of the pandemic. All samples used to come from different states and districts and from long distances. We worked on the diagnosis of COVID samples throughout the day, almost 18 hours per day, even though we knew the COVID virus was dangerous and spreading via air. We were scared, but if we didn’t work—we who knew the proper method of handling a pathogen and a parasite—then who would? So, we shifted our work to COVID. For almost 1 year, we worked on the diagnosis of COVID for the kit and vaccine development. So, the COVID attack shifted our area of focus to viruses, specifically infectious diseases. 

Pharma Now: On behalf of our audience, I thank you for working on the vaccine. Working for 18 hours is a really huge thing and I really appreciate the kind of work you did during the COVID period to contribute to the well being of India. So, what did the 18-hour shift look like? What kind of inspections did you do and what challenges did you face at that time?

Dr. Neeradi: During COVID, we saw so many people die, so many people worried due to disease, and so many deaths because of fear. So looking at these, we thought “We have to work like an engine. We have to do something. We are into science. The Government is giving us an opportunity to apply the knowledge we have found.” With that initiation, we took the work because huge samples were coming and there were very few of us. But if we went out, we saw that people were dying and that made us work those 18-hour shifts. We took some breaks but nothing outside. 

These days, we work for some time and then go watch a movie or go on an outing. But at that time, nothing was there, and there was no space to spend time. People were afraid, even the situation was very dangerous, so where could we go? So, we spent our entire time and energy on COVID diagnosis. We worked for 18 hours, and we used to analyse 5,000 samples per day and that was still much less than needed. We had 80,000, but we could test only 5,000 because there were only a few people on the team. That's how we worked during the COVID pandemic.

Pharma Now: Dr. Dinesh, you mentioned that you created around 80,000 samples but tested only 5000 of them. What was the reason behind it: Was it the technology that made you lag behind? What scope and innovations do you think you could have done?

Dr. Neeradi: Mainly, the diagnosis happened in the initial stages only by reverse transcription polymerase chain reaction (RT-PCR). Right now, we have a kit which gives results in 1 minute. But, at that time, there was no kit. So. RT-PCR was the only solution. Unfortunately, with RT-PCR, for every sample if you want to run in one plate, it takes 3 to 4 hours. At that time, we had only 2 to 3 machines at the Center of Cellular and Molecular Biology for a research purpose. During COVID, thousands of samples were coming, and the capacity of these machines was very low, and the time was also limited. 3-4 hours for one cycle, so per day we can do a maximum of 8 to 10 cycles. The limitation of the RT-PCR method, the number of people and the instrument—especially at that time we had only 3 to 4 machines—limited us. 

Then, the Government approached companies and they provided us 5–6 more machines. So, we could work for maximum 5000 samples. Then, the Government asked us to train more people. We called all government officers, medical officers and doctors and we trained them. Then, they started diagnosing in districts, and that's how slowly the diagnosis started across the state. 

Pharma Now: We also know that you contributed to the development of the malaria vaccine and the COVID vaccine. Can you please tell us more about it?

Dr. Neeradi: We worked on the Malaria vaccine. And, using the same methodology and same research method, we started working on the COVID vaccine. In the initial stages, we found various proteins of the virus which are antigenic in nature (which are identified by the body) and started expressing recombinant proteins; so, we could make them into a vaccine. In the initial stages, we worked on vaccine discovery. But our limitation was the facility, specially we needed a BioSafety Level 4 (BSL-4) facility for that. So, BSL-4 means we were under negative pressure. It will always go from the inside to outside because it is contagious, so BSL-4 facilities. Due to many limitations, the Government gave this project to Bharat Biotech. Bharat Biotech started working on it and finally launched Covaxin. So, that's how I was involved in the basic research of the COVID vaccine, and I am happy to have been a part.

Pharma Now: It’s fascinating to hear how vaccines are developed! I’m sure many people don’t know how much work goes behind one simple vial. But, from what I understand you were a scientist. So, how did your journey take from a scientist to an entrepreneur, and what was the root cause behind it?

Dr. Neeradi: So when I was working in the laboratory, there were certain limitations: limitation of funds, limitations of technology and others. So, I thought: “I have done all the degrees like bachelors, masters, PhD, and postdoc. Why can't I start my own company?” 

When you are working in an organisation, you have certain limitations. You can't go beyond a limit. So, I started my own company Masters Pharma Solutions. Masters Pharma Solution was started in 2010 to make NIPER well known. When I entered NIPER, people in Southern India didn’t join because of lack of awareness. So, I started Masters Pharma Solutions as a platform to spread information to southern states like Andhra Pradesh and Telangana. After completion of my research work, I again started working on Masters Pharma Solutions and created my startup in different fields like pharmacovigilance, medical coding, clinical data management and all the other entries like drug inspector and pharmacist. 

Today, almost 52-55 drug inspectors working across the country in the government sector are my students. In Telangana, almost 25 members are working as drug inspectors. Some are very happy to announce that because they are the regulatory people who regulate the medicine and inspect medical shops and industries. So, we help them to achieve that position. Now, they are working in the government sectors and are very happy. We are also working on pharmacovigilance right now. We are training people in different sectors like the pharma IT sector, where more opportunities are coming in the next few years. We are going to announce on different platforms about opportunities for youth. So, that's how I started my startup, and it is now growing. Let's see how it goes.

Pharma Now: I think it is really a proud moment to see your students working in different organisations. So, moving on, what is the key message you want to give to pharma aspirants and those who want to start their career in the pharma industry?

Dr. Neeradi: I want to say: be determined, be to the point, and don't be scattered. Whichever area you want to work in, be determined about it and stick to that area. Work hard, acquire knowledge so you can break out. First acquire knowledge. Then have a plan and have a vision of where you want to work, which area you want to work in. There are so many platform that will support you, but you must have that level of knowledge and understand concepts. Nowadays, one can flourish because everything is in hand. If you want anything, you can get it. But you should have a proper plan, vision and determination. Technology will support you, people will support you, the government will support you. But you must have some ideas, you have to do hard work. You cannot become a team maker in a night. You have to work hard, you have to choose different areas and obviously you can win the game in any area.

Pharma Now: So, that’s Dr. Neeradi’s key message: Be determined, be to the point and don’t be scattered. I think students will definitely understand this point. It is very important to have knowledge and determination. Dr. Neeradi, it was really great to have you here. Thank you very much for joining Pharma Now.