The lab had earlier found that the serotonin receptors are sensitive to cholesterol surrounding them. In the new study published in Science Advances, they report a sensor region on human serotonin1A receptor that can detect cholesterol. They looked at specific regions called CRAC motifs in the receptor. These are believed to interact with cholesterol. The researchers carefully replaced specific amino acids in the CRAC motifs of the serotonin1A receptor and identified a particular amino acid responsible for the cholesterol-sensitive function of the receptor.

The researchers collaborated with Dr Jana Selent’s group from Pompeu Fabra University Hospital del Mar Medical Research Institute in Barcelona, Spain to visualize the protein-cholesterol interaction via computer-aided molecular dynamics simulations. This helped them predict how the specific amino acid on CRAC motif enables the receptor to sense changes in cholesterol levels by controlling molecular motion in certain regions of the receptor, says CSIR-CCMB statement.

“These findings are important since cholesterol levels change in our cells with age and in many disease conditions.  We believe our work will help in developing better drugs that keep in mind not just the receptor as the drug target, but also the lipid environment in which the receptor is present”, explained Prof Chattopadhyay.

“Our expertise in structural biology at CCMB is key towards a physical understanding of cells and their functions. This not only adds to the detailed view of living cells but also have immense potential in therapeutics development”, said Dr Vinay Nandicoori, Director, CCMB. (India Science Wire)

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Keywords: Molecular, sensor, serotonin, receptor, cholesterol, Cells, receptor proteins, cell membranes, drug target,physiology CSIR-CCMB, drug designing

Presently, colon cancer gets detected at very late stages. There are two techniques to detect it; either CT colonography and colonoscopy or immunohistochemistry. While CT colonography involves low dose radiation, colonoscopy is an invasive process whereas immunohistochemistry can be subjective and sometimes not reproducible.

A new collaborative study involving four institutes in India and one in France, and led by Dr.SagarSengupta at the National Institute of Immunology (NII),has discovered a new way that could identify the disease even at Stage I, the earliest stage.

Dr.Sengupta’s laboratory works on microRNAs, which are small single-stranded non-coding RNA molecules, silence the expression of many proteins. The microRNAs are known to bind to the messenger RNA molecules that code for the proteins and thereby either inactivate or destroy them.

The new study has discovered that six micro RNAs get upregulated in colon cancer cells and that the levels of these were controlled by a master regulator protein, named CDX2. Importantly, the upregulated microRNAs, which were named `DNA damage sensitive microRNA’s or `DDSM’s, were  found to target a group of cellular proteins  which are essential to  maintain the pristine nature of genetic material within each cell of the body. Experiments involving laboratory mice confirmed that the cells have a greater tendency to form cancers if there is over expression of these microRNAs and consequent loss of these genome stabilizers.

The researchers have tested their findings on publicly available datasets in The Cancer Genome Atlas (TCGA) and also in a cohort of colon cancer patients who had come to All India Institute of Medical Sciences (AIIMS), New Delhi for treatment. Analysis was done with the available data of over 410 patients and the biopsy materials of 54 patients from AIIMS, New Delhi.

They found that the DDSMs were upregulated even in Stage I colon cancer tissues. The upregulation persisted upto the final Stage IV colon cancer. More importantly, increased expression of the DDSMs in cancer patients decreased the probability of their survival.

Speaking to India Science Wire, Dr.Sengupta said, “We believe that the identified DDSMs can serve as an invaluable biomarker for colon cancer early detection process. We now have to determine whether the DDSMs can also be detected in patient blood samples. If that is possible, it would make colon cancer detection as simple as the detection of blood sugar in diabetic patients”.

Apart from NII and AIIMS, New Delhi, Regional Centre for Biotechnology, Faridabad, St. John’s Research Hospital, Bengaluru and University of Strasbourg, France contributed to this study. A report on the work has been published in the Journal of Cell Science.

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keywords:CT colonography, colonoscopy, immunohistochemistry, radiation, invasive process, National Institute of Immunology, NII, microRNAs, protein, cellular, experiment, mice,  genome stabilizers, The Cancer Genome Atlas, TCGA, All India Institute of Medical Sciences, AIIMS, biopsy

A new study at the Population Biology Laboratory at Indian Institutes of Science Education and Research (IISER)- Pune promises to help decipher this and several other similar mysteries.

The scientists at IISER,YashrajChavhan, SarthakMalusare, and SutirthDeyconducted their study on E Coli bacteria. They grewsamples of the bacteria with varying population sizes across different environments and then subjected them to whole-genome, whole-population sequencing analysis. They found that samples with a small population size acquired a certain set of mutations which allow them to survive in a certain environment but not in others.

Samples with large populations also developed these mutations. However, they further developed some certain compensatory mutations that together helped them to survive in multiple environments. It was clear that population size determined the kind of mutations available to the bacteria, which in turn, leads to the type of fitness they acquire.

The group studied about 480 generations of E. coli in four types of steady environments consisting of different carbon sources, namely, galactose, thymidine, maltose and sorbitol, and one fluctuating environment in which the carbon source changed unpredictably amongst the four sources.

The study assumes importance as so far it was understood that the ability of a bacteria to develop multi-drug resistance was based on what was termed as `fitness cost’: when bacteria become fit in one environment, they either lose fitness or fail to increase fitness in other environments. The new study has clarified this by showing that when the environment is fluctuating, large populations can bypass this effect.

However, the research work only shows that large population size can help in fluctuating environments. It is not yet clear as to what is the cut-off size. It willvary from one species to another. It would be interesting to figure them out for different kinds of organisms. The scientists have published a paper in the journal `Ecology Letters’.

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Keywords: public health, bacteria, mysteries, E Coli bacteria, population, environment, whole-genome, sequencing, analysis, mutations, survive, generation, carbon sources, galactose, thymidine, maltose, sorbitol, fitness cost, cut-off size.

“The guidelines provide detailed protocols that include pictorials and frequently asked questionsfor an easier understanding of those collecting samples for COVID testing in wildlife”, said Dr. Vinay K Nandicoori, Director, CSIR-CCMB.

LaCONES started testing animal samples for possible SARS-CoV-2 coronavirus infection in August 2020. The scientists found the first positive samples from Asiatic lions in Nehru Zoological Park, Hyderabad in April 2021. During these days, LaCONES team has tried testing for coronavirus using different kinds of nasal, oropharyngeal, rectal and fecal samples from the animals. LaCONES regularly tests wildlife samples using DNA-based molecular biology tools to solve wildlife cases. These tests are very similar to the ones being used for coronavirus testing.

“We hope that our recommendations help the zoo staff in collecting and packing the samples appropriately before they send them out to animal testing centres, will smoothen the process for the zoos as well as testing centres. Given how difficult it is to get samples from animals, it is all the more important that we make most of the samples we get”, said Dr. Karthikeyan Vasudevan, Scientist-in-charge, LaCONES, CSIR-CCMB.

Keywords: LaCONES, CSIR-CCMB, CSIR, COVID-19,Zoo Animals, Captive Animals, Laboratory for the Conservation of Endangered Species, Centre for Cellular and Molecular Biology,Coronavirus Infection, Central Zoo Authority, Ministry of Environment, Forest and Climate Change

This could pave the path towards understanding the probable role of the virus in neurodegenerative pathologies, especially given the fact that the virus has been detected in brain tissue of the patients suffering from neurological disorders such as Alzheimer’s, Parkinson and multiple Sclerosis.

The EBV can cause cancers like nasopharyngeal carcinoma (a type of head and neck cancer), B-cell (a type of white blood cells) cancer, stomach cancer, Burkett’s lymphoma, Hodgkin’s lymphoma, post-transplant lymphoid disorders, and so on. More than 95% of the adult population is positive for EBV. However, the infection is mostly asymptomatic, and very little is known about the factors which trigger the development of such disease. It was the detection of the virus in patients with neurodegenerative diseases that triggered the search for the mechanism of propagation of the virus.

Scientists’ teams from the Departments of Physics (led by Dr. Rajesh Kumar) and Biosciences and Biomedical Engineering (Dr. Hem Chandra Jha) at IIT Indore along with their collaborator, Dr. Fouzia Siraj, at National Institute of Pathology (ICMR), New Delhi, used Raman Spectroscopy System supported by “Fund For Improvement of S&T Infrastructure (FIST)” scheme of Department of Science and Technology to trace the propagation mechanism of the virus. Research scholars Ms. Deeksha Tiwari, Ms. Shweta Jakhmola, and Mr. Devesh Pathak also contributed to this study published recently in the journal ‘ACS Omega’.

The phenomenon of Raman Scattering, first discovered by Indian Nobel laureate (awarded by Bharat Ratna) Sir C. V. Raman, provides information on the structure of any material based on the vibrations produced in them. Similarly, the light falling on the virus generates vibrations in the biomolecules, depending on the make of the virus. Using RS, the light that is scattered by the virus can be captured and analyzed to understand its structure and behaviour. Interestingly, every virus has a different biomolecular composition and thus generates a unique Raman Spectrum that serves as a fingerprint to its identity.

Dr. Jha’s and Dr. Kumar’s team have elucidated the infection pattern of EBV in the brain cells showing that the virus is also capable of infecting the glial cells (astrocytes and microglia) in the brain. This study noticed a differential pattern of infection progression in different glial cells. Dr. Jha said, “We found that the virus may take different time intervals to establish and spread infection in various types of glial cells of the brain.” Apart from the timeline of infection progression, their team also tried to reveal the biomolecules involved at each step of the virus infection and relate it to various neurological manifestations.

Dr. Rajesh added, “Our study showed that molecules like phospho-inositols (PIP), a type of lipid, glycerol, and cholesterol, are predominantly altered during EBV infection in the brain cells.”

The study, based on spatial and temporal changes in Raman signal, was helpful in advancing the application of Raman Scattering as a technique for rapid and non-invasive detection of virus infection in clinical settings. Since all the techniques available for viral load detection in the brain by far include invasive methods, RS can be a sigh of relief for patients undergoing brain biopsies for diagnostic purposes. Furthermore, it can be helpful in determining the stage of infection based on biomolecular markers and thus aid in early diagnosis.

Cryo-EM has revolutionized structural investigations of macromolecules in recent times. It is a testimonial for a revolutionary technology for structural biologists, chemical biologists, and ligand discovery, which has gained a clear edge over contemporary x-ray crystallography. In light of these advancements, cryo-electron microscopy technique was recognized with the Nobel Prize for the high-resolution structure determination of biomolecules in solution (2017). The revolution in resolution resulted in atomic-level understanding of the Zika virus surface proteins, thus aiding structure-based drug discovery, deciphering of structure of hard-to-crystallize membrane proteins and other macromolecular complexes.

The National Facilities supported by the Science & Engineering Research Board (SERB), an institution under the Department of Science & Technology (DST), would help explore Macromolecular Structures and Complexes” and create research knowledge base and skills for cryo-EM research in India to establish leadership in structural biology, enzymology, ligand/drug discovery.

The establishment of these facilities in all directions of the country–Indian Institute of Technology, Chennai; Indian Institute of Technology, Bombay; Indian Institute of Technology, Kanpur; and Bose Institute, Kolkata would help in scaling up cryo-EM based structural biology research in different corners across the country. These centers are designated as SERB National Facility for Cryo-Electron Microscopy and will work on the identified thrust areas. They will be accessible to all researchers.

Housed with 200kV machines have added advantages like lesser maintenance and can help generate human resources through training, which can also help sustain the facility for longer duration. Each Cryo-EM facility costs about Rs. 28.5 crore for a period of five years and an amount of Rs. 114 crores for research in the critically important research areas.

While IIT Chennai will focus on nano-biointerfaces (e.g. materials–microbes, materials–human tissue), IIT Bombay will execute research on ribosome translation and its implication in disease and antibiotic resistance, neurodegenerative disorders and tackle problems to address solutions to cancer, membrane structure, composition, dynamics & transport. IIT Kanpur will conduct research focused on macromolecular structures and drug discovery with a specific focus on membrane proteins, and Bose Institute, Kolkata will focus on transforming the structure-guided drug discovery and therapeutics research for communicable and non-communicable diseases, allosteric drugs, transcription, and epigenetics.

The first national cryo-EM facility was established at National Centre for Biological Sciences (NCBS) in 2017 and then subsequently in IISc, Bangaluru, and RCB Faridabad. However, it was felt that the existing cryo-EM research facilities in the country are not adequate to leave a mark at the global stage. Historically, Indian scientists have contributed significantly in the area of Prof. GN Ramachandran and Dr. G. Kartha made a remarkable contribution to structural biology, biological, chemical, physical, computational, and theoretical crystallography and materials crystallography. Given significant advances in cryo-EM of large structures, SERB has taken the responsibility that concerted funding should be provided to establish leadership in this area to enable and empower Indian researchers to lead from the front.

The manufacturing complexity is a major reason for the therapy cost. In order to promote and support development of CAR-T cell technology against cancer and other diseases, BIRAC and DBT have taken initiatives and launched specialized calls to invite proposals in the last 2 years.

The 4th June, 2021 was a historic day for TMH, IIT Bombay team and cancer care in India as the first CAR-T cell therapy (a type of gene therapy) was done at the Bone Marrow Transplant unit at ACTREC, Tata Memorial Center in Mumbai. The CAR-T cells were designed and manufactured at Bioscience and Bioengineering (BSBE) department of IIT Bombay.

This work is partly supported by BIRAC-PACE scheme. The TMC-IIT Bombay team are further supported to extend this project for conducting Phase I/II trial of their CAR-T product by DBT/BIRAC, through National Biopharma Mission.

This is a “first in India” gene therapy in early phase pilot clinical trial and the dedicated efforts and excellent collaboration between IIT Bombay and Tata Memorial Hospital, Mumbai.The central government’s National Biopharma Mission-BIRAC has approved 19.15 Cr crore to the team for conducting a first-in-human phase-1/2 clinical trial of the CAR-T cells. The clinical trials are being done by Dr (Surg Cdr) Gaurav Narula, Professor of Paediatric Oncology and Health Sciences, and his team from TMC, Mumbai, and the novel CAR-T cells that will act as drugs that were manufactured by Prof Rahul Purwar, Bioscience and Bioengineering (BSBE) department and his team at IIT Bombay. The design, development, and extensive pre-clinical testing was carried out by IIT-B as a collaborative project with Tata Memorial Center, Mumbai by the two Investigators.

IIT-B director Subhasis Chaudhuri said this was a significant feat for the institute as well as the country. “We at IIT-B are delighted that our scientists along with Tata Memorial Hospital have come out with the most sophisticated therapy in cancer treatment. If the trials are successful, it may save millions of lives by making the treatment available in India at an affordable cost. It is a research of IIT-B that is expected to touch the lives of all,” said Chaudhuri.

National Biopharma Mission is also supporting the development of Lentiviral vector manufacturing facility for packaging plasmids used to transfer the modified T cell inside the body, cGMP facility for T-cell transduction and expansion for CAR T-cell manufacturing to two other organizations. The development of CAR-T cell technology for diseases including acute lymphocytic leukemia, multiple myeloma, glioblastoma, hepatocellular carcinoma and type-2 diabetes is supported through DBT.

As researchers, industrialists and entrepreneurs synergized their capabilities and efforts to fight this massive battle at all fronts, several science-based startups brought out new technologies, repurposed their existing technologies, scaled up operations, and commercialized them with support from the government.

Existing capability, infrastructure and resources were managed judiciously to increase the production capacity for PPE kits, masks, testing infrastructure, and research for vaccines to empower the country during this period .

Financial support from the Technology Development Board (TDB), a statutory body of the Department of Science and Technology, helped several startups to commercialize their products like testing kits, masks, sanitisers, thermal scanners, and medical devices to bring about meaningful contributions in India’s fight against COVID 19. It was triggered by invitation for proposals from companies specifically seeking solutions for fighting COVID 19 pandemic for providing financial support. Encouraged by invitation, several startups put in innovative proposals which helped commercialize a range of technologies by tiny science-based startups and bring innovative solutions to fight the pandemic.

Pune-based Mylab Discovery was the first indigenous company to have developed a real-time PCR-based molecular diagnostic kit that screens and detects samples of people who display flu-like symptoms. The kit was developed, approved by ICMR and CDSCO, and deployed in a very short time . With support from TDB, production of kits was ramped up in short span of time from 30,000 tests to 2 lakh tests per day.

Further, the company has developed a highly sensitive antigen kit and reached more than 2 crore Indians in remote areas who did not have access to RT-PCR testing as well as Compact XL to automate RT-PCR testing and resolve delays and errors in diagnostics for millions of Indians. The company also designed special labs and took them to interiors of Maharashtra, Goa, and many parts of the country and deployed Mobile RT-PCR Labs in Rural and Urban Areas during the second wave.

Mylabs, which has recently developed a home testing kit called “COVISELF”, India’s first self-test kit and ramping up its commercialization, has emerged as a Unicorn during this crisis and is expected to further play a critical role with respect to testing for COVID 19.

“Science and Technology are best when they create a seamless, end-to-end chain of value from knowledge creation to knowledge consumption, from R&D to innovation to the creation of new socio-economic opportunities. The stories of commercialization of the Indian tech products of relevance by the timely support of TDB brings to fore the last mile translation of knowledge to new opportunities,” said Prof Ashutosh Sharma, Secretary, DST.

RTPCR test Kit: PathoDetect                Rapid Antigen test Kit: Pathocatch

Mobile RT-PCR Labs                           Self Diagnostic Kit: Coviself

M/s Mylabs Discovery Pvt. Ltd., Pune Products

A Delhi-based company called Nanoclean Global has assembled and installed the semi-automatic N95 mask production machine and started commercial-scale production of N95 masks. The company, which has distributed one lakh N95 Masks to the Delhi Police, has supported India’s fight against COVID 19 by manufacturing and providing more than 3.0 lakhs N95 masks for the citizens.

N 95 Masks for Delhi Police

Pune-based Thincr Technologies India developed low-cost and efficient masks coated with antiviral agents to protect spread and protection of COVID-19 and other viral infections. They are also involved in the coating and 3D printing of anti-viral agents on the masks as a preventive measure against COVID-19. Having commenced commercialization of its masks, they have distributed 6000 antiviral coated masks to various Government Organizations across the country.

Antiviral Masks distribution through NGO to various Organizations

Evobi Automations, Bangalore has developed Ultraviolet Sanitizers in two different models, one of which is portable and distributed in various hospitals in Mumbai, Pune, and various Government schools across the country. They have sold more than 500 UV Sanitizer boxes and are receiving orders from various organizations.

Distribution of UV Sanitization Boxes to various Organizations

A Portable X-Rays machine with Digital Imaging and Battery Back-Up has been developed by Coimbatore-based Iatome Electric India, which is of considerable support in the isolation wards and Intensive Care Units of the COVID 19 management set-up. It can facilitate X-ray imaging in remote & rural locations with limited or no power. It has also deployed the first version of the digital Chest X-Ray machine for trial in hospital setting.

Trials of Mobile Digital X-Ray

Pune-based Briota Technologies have developed a cost-effective digital handheld spirometer called “SpiroPRO” useful for measuring and monitoring lung capacity, diagnosing lung infection, and its effect on lung capacity. The product comes with a Mobile App, NEHA (Nurse Educator and Health Assistant), to assist during monitoring of lung condition and managing Ventilator support with telemedicine/tele counselling facility.

The company, which was amongst the top finalists at the 11th edition of Aegis Graham Bell Award under Innovative diagnostic solutions, developed a questionnaire-based App called ‘SAVE’ that was provided to MCGM (Mumbai Municipal Corporation) and some private players to check the spread of COVID among its poorer population. More than 100 people could get emergency medical help from MCGM and hospitals, based on the score of this App. The ones with medium symptoms were connected to doctors via video conferencing.

Handheld Spirometer: SpiroPRO; M/s Briota Technologies Pvt Ltd, Pune

Bangalore-based Cocoslabs Innovative Solutions developed and commercialized a high-accuracy and contactless thermal analytics product for detection of elevated body temperature along with automated checking for face masks and social distance compliance. In India, it is the first company to launch a thermal analytics solution in India for automatic temperature checking in free-flow crowds, thereby eliminating waiting time and exposure risks. The solution can screen over 10,000 people in a single day with a single unit when deployed in crowded places like railway stations, airports, bus stands, government offices, hospitals. It can also detect people not wearing a mask or improper mask-wearing.

The funding support from TDB allowed the company resources to be freed for working on new solutions. The company, which also has contactless attendance with face recognition along with thermal analytics up their kitty, is currently working with other companies that are looking to set up post-COVID compliance protocols by using this solution to reopen their offices. They are working on AI-sensor for hospitals that will monitor oxygen levels in oxygen tankers and alert authorities well in advance to enable better planning by obtaining oxygen availability data in real-time and ensure equitable supply at critical times.

Thermal Scanning Camera                  Software Output Image

M/s Cocoslabs Innovative Solutions Pvt. Ltd., Bangalore.

Current COVID-19 treatments simply manage symptoms while the body fights off the infection with its immune defence system. There are, as yet, no confirmed antiviral drugs that can stop the virus from replicating. One route to neutralising any virus is to attack its proteins; such an approach holds true for the COVID-19 virus as well and scientists across the globe are involved in studies to elucidate the structure and functions of these proteins to understand the viral disease and develop drugs that are effective against the virus.

“From a conformational or ‘shape’ point of view, several proteins contain ordered and intrinsically disordered regions. These classical conformations are in the proteins in the SARS-CoV-2 virus as well. The structure of non-structural protein 1 (NSP1) is composed of 180 amino acids. The first 1-127 region has been experimentally shown to form an independent structure by Clrak, Green & Petit from University of Alabama. However, there was no experimental proof given by any group on the 131 to 180 amino acid regions of this NSP1 protein, which plays a key role in suppressing the host immune system. With the support of Circular Dichroism spectroscopy and Molecular Dynamics Simulations our group at IIT Mandi has deciphered the conformation of this region in isolation.”, explained Dr. Rajanish Giri, Assistant Professor of Biotechnology, IIT Mandi.

This virus has sixteen non-structural proteins (NSP1–NSP16), of which, the NSP1 plays a vital role in the pathogenicity (ability to cause disease) of the virus.  The NSP1 disrupts the proteins of the host cell and suppresses its immune functions. Its importance can be understood by the fact that it is also called the ‘host shutoff factor’. Particularly Nenad Ban and colleagues have found that if the C-terminal region of NSP1 i.e. 131-180 residues are removed from NSP1 then NSP1 is unable to stop the translation by ribosomes. It is therefore important to understand the molecular mechanisms, biophysical interactions, and chemistry of the interplay of the NSP1 with the host cell.

“Earlier in 2020, we have shown through bioinformatics studies that NSP1 C-terminal region has intrinsic disorder propensity between 0.4 to 0.5 scales, i.e. very close to borderline of intrinsic disorder prediction. However, without experimental studies we were not sure that this 131-180 amino acid region is actually an intrinsically disordered protein region. Generally, these regions are unfolded in solution but are folded into particular conformations when binding with specific molecules or partners inside the host cells”, said Dr. Giri.

The IIT Mandi team has experimentally studied the structural conformations of SARS-CoV-2 NSP1 under various conditions – in an organic solvent, membrane mimetic environment, and inside liposomes. Using analytical techniques such as circular dichroism spectroscopy, fluorescence spectroscopy, and molecular dynamics simulations, the researchers have shown the dynamic changes in the conformation of the IDR of the NSP1, in response to its surroundings, due to hydrophobic and electrostatic interactions between the protein and the environment.

“Our finding provides valuable insight into disorder-order conformation of the NSP1 C-terminal region (residues 131-180) of the SARS-COV2 virus under various environments, which will help in understanding the broader aspect of NSP1 and its interactions with binding partners that are currently unknown”, said Dr. Giri.

Understanding the conformational structure and associated functions of key viral proteins such as the NSP1 can eventually help develop therapeutics that can target these proteins and stop the virus in its tracks. Studies such as those conducted by Dr. Giri and his co-workers can bring this approach closer to reality.

This study has been published in the journal ‘Current Research in Virological Science’, in a paper co-authored by Dr. Giri and his research scholars, Mr. Amit Kumar, Mr. Ankur Kumar and Mr. Prateek Kumar, along with Dr. Neha Garg from the Banaras Hindu University.

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Keywords: Protein structure, COVID-19, Coronavirus, Indian Institute of Technology, IIT Mandi, Antiviral, therapeutics, ICMR, MoHFW

The current COVID-19 pandemic is a grim testimony to the damage an infectious disease can cause to human health and welfare. A major challenge in treating such diseases is misdiagnosis, which can lead to trial-and-error treatments, and improper use of antibiotics. Identifying the correct type of infection is therefore critical, say IISc statement.

The human body responds to bacterial and viral infections differently. It produces different types of molecules ‒ such as proteins and RNA ‒ in the blood, depending on the type of infection. While antibiotics can treat bacterial infections, they are ineffective against viral infections. However, indiscriminate use of antibiotics to treat any kind of infection has given rise to bacterial strains that are now resistant to our entire arsenal of antibiotics. “Antibiotics are given even for viral infections in some cases because of misdiagnosis. With current methods, it can take a lot of time to test for bacterial or viral infections,” explains first author Sathyabaarathi Ravichandran, Research Associate in the lab of Nagasuma Chandra, Professor at the Department of Biochemistry.

A quick method to detect acute viral and bacterial infections and distinguish between them can be immensely useful in the clinic, as accurate diagnosis will win half the battle and guide the clinician towards the optimal treatment path. It will also prevent the rise of such antimicrobial resistance. In the new study, published in the journal EBioMedicine, the researchers have developed such a test using patient blood transcriptomes and sophisticated computational modelling.

A transcriptome is a full set of mRNA molecules expressed by a biological cell, which is measured using Next-Generation Sequencing (NGS) technologies. During an infection, there are specific genes that get turned on and these in turn lead to higher amounts of specific mRNAs and ultimately higher amounts of the corresponding proteins. The scientists analysed transcriptomic data of patients (from publicly available databases, and samples collected from MS Ramaiah Medical College in collaboration with a clinical team) and discovered a ten-gene RNA signature in the patients’ blood that is produced in varying quantities for viral and bacterial infections.

To make it useful in the clinic, the researchers devised a standalone score called VB₁₀, which could be used for diagnosis, monitoring the stage of recovery after infection, and estimating the severity of the infection. VB₁₀ accurately indicated whether a given blood sample had a bacterial or viral infection, across different bacteria and viruses and across different age groups.

The authors suggest that the test could be useful for differentiating COVID-19 infection from bacterial infections as well. In the study, they looked at various viral infections for which transcriptomic data is publicly available. This allowed them to develop a generic VB₁₀ test score for viral infections. As soon as transcriptomic data became available for COVID-19, the team tested their approach and found that the test scores could differentiate between SARS-CoV-2 infection and common bacterial respiratory infections.

This work was done in collaboration with clinicians at MS Ramaiah Medical College and researchers Amit Singh, Dipshikha Chakravortty and KN Balaji at IISc. The team hopes to begin a trial study to translate their research from the lab to the clinic. “This test can be done using qRT-PCR. Given how common RT-PCR has become due to the pandemic, getting this test off the ground should not pose a major challenge,” says Chandra. The researchers expect it to be useful early on during the infection, and work against any strain.  This can supplement the current COVID-19 diagnosis tests.

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Keywords: The Lancet, Indian Institute of Science, IISc, Molecular, Biomarkers, Differential diagnosis, Bacterial, Viral, Infections, mRNA, Molecules, Blood, COVID-19, Pandemic Infectious disease, Health