1. AI Technique for early detection of COVID-19 infection be detecting of lung abnormality from chest CT-Scan for initial days
The existing (popular) test for COVID-19, namely RT-PCR has high specificity but low sensitivity. Hence, there may be many False-Negative (as low as 60%). It is therefore necessary to have yet another test to reinforce the detection process minimizing the negative cases. It is established in multiple publications that Ground Glass Opacity (GGO) is one important feature for lung abnormality detection from chest CT scans. But depending on only GGO feature will not be enough to correctly detect abnormality in lungs due to COVID-19. The most discriminating features for COVID-19 pneumonia include “peripheral distribution”, GGO, and “Vascular Thickening”.
Some authors observed that CT scan for Lungs is no good because though there can be many individuals with COVID-19 having abnormal lung functioning, though there are sizeable number of persons with normal lung functioning have possibly infection. We feel these observations are due to the absence of rigorous investigations of recognition algorithms.
There are publications which show the possibility of detection of pulmonary GGO using AI techniques in earlier contexts of lung abnormality (in the context of cancer). IIT/Patna is also investigating in these lines. We propose a multi-channel deep learning framework for robust detection of lung abnormality due to COVID-19. We plan to use one channel for RoI determination of CT-Scan images, followed by two parallel channels. One channel for 2D CT scan images for GGO detection. In parallel, there is another channel to analyze the 3D shape for vascular analysis. The outcomes of these two parallel channels meet at yet another stage where we propose to carry out a temporal analysis of CT scans over multiple days to detect thickening and crazy paving. Such a detailed analysis can be a robust, we believe, detector of COVID-19. Initial experiment of our deep learning architecture on public dataset of Lung CT Scan is very promising.
Researchers- Dr Vikas Kumar (CURaj), Dr Venkateswara Kagita (NIT Warangle), Dr Arun K Pujari(CURaj)
2. A mathematical model for host-parasite coevolution: Role of selection, mutation and asexual reproduction
The key to the survival of a species lies in understanding its evolution in an ever-changing environment. We report a theoretical model that integrates frequency-dependent selection, mutation, and asexual reproduction for understanding the biological evolution of a host species in the presence of parasites. We study the host-parasite coevolution in a one-dimensional genotypic space by considering a dynamic and heterogeneous environment modeled using a fitness landscape. It is observed that the presence of parasites facilitates a faster evolution of the host population towards its fitness maximum. We also find that the time required to reach the maximum fitness (optimization time) decreases with the increased infection from the parasites. However, the overall fitness of the host population declines due to the parasitic infection. In the limit where parasites are considered to evolve much faster than the hosts, the optimization time reduces even further. Our findings indicate that parasites can play a crucial role in the survival of its host in a rapidly changing environment.
Researcher- Dr Manish D Shrimali (CURaj)
3. Flexible Nose Filters
Air pollution is a major environmental risk to public health. Risk of bacterial and viral diseases including Covid-19 is very high these days. Further, people living in urban areas tend to be more susceptible to adverse effects of air pollution particularly respiratory illnesses. Reducing air pollution remains a challenging task. Face masks are widely used to protect most airborne particles from being inhaled. However, the face mask feels uncomfortable because everyone's face has different facial features. Further it is difficult to block different air borne particles through a face mask. Moreover, it is not welcome or encourages wearing a face mask in public places, like school, office or hospital. Further when the facemask is wet by rain water, it becomes sticky causing the user to become uncomfortable. Therefore, it is essential to seek for user’s friendly and advanced air pollution control methods for filtering airborne pollutants.
Considering the limitations and disadvantages of the related face mask and available nose filter, the present invention provides an improved intrusive-style nose filter to overcome the limitations and unpleasantness associated with prior art. The proposed invention utilizing the high surface area and high porosity of polymeric nanomembranes, significantly increase flux and reduce transmembrane pressure drop making it effective against breathing against dense air pollution. Another aspect of the present invention relates to negatively and positively charged filters for removing a wide range of airborne pollutants. The present invention further relates to a flexible housing to hold the disposable filters. The wall of filter housing consists of several layers of ring shaped structure, preventing collapse during inhalation and thus keep the airway open for improved breathing.
The nose filter of the proposed invention is designed to be inserted near to a nostril and includes a flexible housing, a filtering component comprising different layers of polymeric membranes. Layers of polymeric membranes may be differently charged filter media along with layers of nanocarbon filter media or other membranes. Further, another objective of the proposed invention is to provide separate provision of exhalation and inhalation chambers within the nose filter that will improve user compliance and breathing experience. Proposed nose filter design will be economical, commercializable and may be an alternative N-95 mask. This will be helpful for providing protection against air pollution and droplet transmission of diseases including COVID-19.
Researcher- Professor Amit Goyal (CURaj)
4. Development of rapid Low-Cost High Precision diagnosis tool for SARS-CoV-2 COVID-19 suitable for small diagnostics lab and health center
Due to the COVID-19 pandemic, the massive number of patients are untested and facing challenges in the screening of the population to control the disease spreading. The current diagnostic tools combine clinical symptoms and molecular methods. Due to the resembles of symptoms with common cold and flu, the accurate molecular result is critical for final diagnosis. RT-qPCR is the gold standard for COVID-19 testing but requires expensive infrastructure and experienced technical staff, time-consuming, and extremely difficult to deploy in small towns and villages of India. Due to the different types of samples containing the variable number of viruses, it is a fear of a large proportion of patients may be diagnosed as false negatives. A rapid, simple, low-cost sensitive, and specific point of care POC molecular diagnostics test for COVID-19 is urgently needed.
The Major aim of this proposal is to develop a COVID-19 diagnostic tool that can further be used as a simple, inexpensive point of care (POC) devices for testing COVID-19 in small labs, remote health centers, and private and government clinics in India. The proposal is mainly focused on Loop-mediated isothermal amplification. LAMP-based methods that have been successfully implemented in other pathogen identifications and also have used in inexpensive and straightforward POC for the diagnosis.
In collaboration with the Institute of Bioinformatics, we did the genome analysis of the SARS-CoV-2 (COVID-19) family. Also, the genome of COVID-19 was compared with other family viruses, including HIV. We have identified genomic regions that are suitable for detection kit development. Interestingly, we also identified two stretches of amino acid sequences that were specifically inserted in one of the COVID-19 proteins. In Silico analysis suggests that these inserts are essential for vial protein oligomerization and stability of the virus. We have compiled the data, and the manuscript will be submitted within a week.
Researchers- Dr Pankaj Goyal (CURaj), Dr. Akhil Agrawal (CURaj), Prof. Sanjiv Maheshwari (JLN Medical College, Ajmer), Prof. Vijaylatha Rastogi, (JLN Medical College, Ajmer), Dr. Abhishek Kumar (Institute of Bioinformatics, Bangalore)
5. Repurposing of FDA approved drugs for potential application towards combination therapy against COVID-19: in-silico screening of molecules and preliminary in-vitro validation
Coronavirus disease is an infectious disease caused due to the infection of severe acute respiratory syndrome coronavirus 2. This disease was first identified in china in December 2019 and is known as coronavirus disease 19 (COVID-19). WHO declared coronavirus disease as pandemic due to community level of spreading of disease. The main symptoms of disease included fever, cough, and shortness of breath. According to WHO report 1 million cases in just 4 month with mortality of fifty five thousand worldwide. Most affected countries are the USA, Span, Italy, Germany & China. WHO declared a coronavirus outbreak a public health emergency of international concern on 30th January 2020 and a pandemic on 11th March 2020. The first case of coronavirus was reported on 30th January 2020 in India and till date 2900 cases reported across the country with mortality of 75.
Currently there is no therapy available for the treatments of coronavirus disease. Due to the pandemic nature of disease and high mortality rate now worldwide researchers started to work on it with great attention to develop treatments, vaccine & diagnostic assay for early detection of infection. Such research are focused on basically developing vaccines, diagnostic and therapy for this disease. We urgently required therapy for the treatment of this disease, as we know development of new drugs for this disease will take much time, so researchers started working on short term goals and long-term goals to develop new therapy. In the short term goal, they started to work with drugs available for the treatment of different diseases. They try to repurpose some selected drug lead obtained by virtual screening against virus target molecules.
In-silico approach of drug screening against molecular targets gets attention for designing new drugs as well as to repurpose existing drugs against COVID-19. Here we proposed to repurpose existing FDA approved drugs against COVID-19 using in-silico drug screening approach against virus proteins. These screened potential molecules will be tested against specific target protein for their inhibition study, binding study using in-vitro study to find out efficacy of the drug against that molecular target.
Researchers - Dr. Shiv Swaroop (CURaj), Dr. Awadh Bihari Yadav (Univ of Allahabad), Dr Pramod Katara (Univ of Allahabad)
6. Pathogenicity Enhancing Structural differences between SARS-CoV and SARS-CoV-2 spike glycoprotein
A new coronavirus epidemic COVID-19 poses serious threat across continents, leading to the World Health Organization declaration of a Public Health Emergence of International Concern. To date, no antiviral drugs or vaccines are available. In order to stop the entry of the virus into human host cells, major therapeutic efforts are now targeting interactions between the SARS-CoV-2 spike (S) glycoprotein and the human cellular membrane receptor angiotensin-converting enzyme, hACE2. By analysing cryo-EM structures of SARS-CoV-2 and SARS-CoV, we have reported here that the homotrimer SARS-CoV-2 S receptor-binding domain (RBD) that bind with hACE2 has expanded in size with a large conformational changes of its AA residues relative to SARS-CoV S protein. Protomer with the up-conformational form RBD that only can bind with hACE2 showed higher intermolecular interactions at the interface, with the inclusion of two specific H-bonds in the CoV-2 complex. However, these interactions have resulted in significant reductions in structural rigidity, favouring proteolytic processing of CoV-2 S protein for the fusion of the viral and cellular membrane.
Researcher- Dr Amit Chakrabarty (Curaj) and others
7. In-Silico Investigation for the Binding of Uniquely Synthesized Fluorescent Fluorinated Amides With 2019-nCoV Main Protease Enzyme: A Potential Chemotherapeutics for treatment of COVID-19
Since the outbreak of SARS-CoV-2 in Wuhan, China during December 2019, COVID-19 has become a global pandemic, a threat to public health across the world. Towards a better understanding for the mechanism of action of the virus, biologists have been able to identify the spike protein as the receptor binding domain for coronavirus 2 and ACE2 (angiotensin-converting enzyme 2) as receptor in human cells. Although several researchers around the world are trying to contribute in different aspects to develop a potential tool to defeat the virus, the struggle for a vaccine and potential chemotherapeutics continues. In an effort to tackle this disease and provide a potential chemotherapeutic, we designed a series of fluorescent fluorinated amides (Fluorinated α-amino amides) (few have been synthesized) and conducted an in-silico investigation for the binding of these compounds with the COVID-19 main protease enzyme (Mpro), an enzyme that plays key role in processing the polyproteins that are translated from the viral RNA and has been recognized as valid drug target to develop anti-SARS drugs. The active site was chosen based on the binding region of the natural inhibitor N3 in COVID-19 main protease-N3 complex. The investigated results showed a very good binding affinity in terms of binding energy and inhibition constant. Further, to compare the investigated data with a known inhibitor of main protease N3, we performed in-silico study for the same and found that most of the investigated compounds (new compounds) were showing better activity than N3. Additionally, the fluorescent property of the studied compounds makes them unique to be used as potential biomarkers for the determination of the status of the inhibitor bound protease and identification of the receptor site in human cells. Importantly, the compounds investigated contain fluorine atoms, which opens the opportunity to potentially utilize the Positron Emission Tomography (PET) technique by introducing 18F in the molecule to understand the underlying biological phenomenon.
Researcher- Dr Ritesh Singh (Curaj) and Anirban Mukherjee
8. High throughput virtual screening approach to identify multi-target inhibitors for COVID-19 treatment
The present-day world is severely suffering from the recently emerged SARS-CoV-2. The lack of prescribed drugs for the deadly virus has stressed the likely need to identify novel inhibitors to alleviate and stop the pandemic. In the present high throughput virtual screening study, we used in silico techniques like receptor-ligand docking, Molecular dynamic (MD), and ADME properties to screen natural compounds. It has been documented that many natural compounds display antiviral activities, including anti–SARS‑ CoV effect. The present study deals with compounds of Natural Product Activity and Species Source (NPASS) database with known biological activity that probably impedes the activity of six essential enzymes of the virus. Promising drug-like compounds were identified, demonstrating better docking score and binding energy for each druggable targets. After an extensive screening analysis, three novel multi-target natural compounds were predicted to subdue the activity of three/more major drug targets simultaneously. Concerning the utility of natural compounds in the formulation of many therapies, we propose these compounds as excellent lead candidates for the development of therapeutic drugs against SARS-CoV-2.
Researchers- Dr V Prajapati (CURaj), Dr Vijaya Verma (CURaj), Dr Dhaneswar Prushti (CURaj)
9. Local Herbal decoction to boost immunity during COVID-19 pandemic
Ayurveda a traditional medical system of India insists on the promotion of health and cure of disease. In many health conditions, Ayurveda recommends herbal decoctions for quick recovery through strengthening the healing process. Ingudi/Hingot (Balanites aegyptiaca Linn. Delile) is a small tree with glabrous or puberulous branches bearing very strong sharp ascending spines and bifoliate leaves of two elliptical or obovate, coracious leaflets. It is distributed in the drier parts of the country in western Rajasthan and peninsular India from south East Punjab to West-Bengal and Sikkim. There had been reference of Ingudi in Vedic texts such as Vishnu-Dharma sutra, Sankara -Dharma sutra and Kalidasa’s Shakuntala. The objective is to investigate efficacy of local medicinal plants as immune booster. Considering the ongoing COVID -19 pandemic we recommend 50 ml decoction of Ingudi, Neem, Tulasi and Pudina with few drops lemon and 1/2 spoon of honey. This decoction would help to boost immunity, reduce inflammation and it has got antioxidant property. These herbs have been widely used in many ways across India and found to be safe and no side effects. We are also interested in investigating the chemical compositions, anti-microbial activity, antioxidant property, and immune-boosting property of these medicinal plants. We also recommend this decoction to be tested on patients during the quarantine stay.
Researcher- Dr Kashinath Metri (CURaj), Dr Sanjeeb Kumar Patra (CURaj)
10. Clinical application of Non-Covalent Inhibitors of the SARS-COV Proteinase (3CLpro) for Coronavirus therapy
A novel coronavirus has been identified as the causative agent of the severe acute respiratory syndrome (SARS). The main viral proteinase 3C-like protease (3CLpro), which controls the activities of the coronavirus replication complex, is an attractive target for therapy. The 3CLpro has proven to be a valuable target in drug discovery efforts and has been validated as a valid drug target against several viruses. It has even been termed “the Achilles’ heel of coronaviruses.
The substrate-binding site of the 3CLpro has two deeply buried S1 and S2 subsites, as well as shallow S1′, S3, and S4 subsites with varying degrees of solvent exposure. The substrate specificity of coronavirus 3CLpro is mainly determined by the P1, P2, and P1′ positions. The P1 position has an absolute specificity for glutamine, which stabilizes the S1 subsite via a hydrogen bond with the imidazole Nε2 of His162/3 and van der Waals interactions with surrounding residues of the S1 pocket. The P2 site has a preference for leucine or methionine to fill the hydrophobic S2 pocket. The sidechains of the S3 site are solvent-exposed, and therefore this site is expected to tolerate a wide range of functionality but shows a preference for basic residues. Sidechains and backbones of residues surrounding the S4 site create a highly congested pocket, which favors a small, hydrophobic residue in the P4 position, either Ser, Thr, Val, or Pro. The S1′ and S2′ subsites also accommodate small residues in the P1′ and P2′ positions, which may include Ser, Ala or Gly. A typical cleavage recognition site is, therefore (Ser, Ala)-(Val, Thr)-Leu-Glu ↓ (Ser, Ala, Gly), which is conserved among all coronavirus 3CLpro.
Significantly, It indicates that virus proliferation might be inhibited using specific proteinase inhibitors supporting the hypothesis that proteinases are indeed crucial during infection. Prompted by this, I set out to analyze and predict cleavage by using ML-188 compound by using in vitro and in vivo studies.
Researcher: Dr. Shailendra Pratap Singh (CURaj)
11. Inhibition of the SARS-CoV-2 replication and nuclear capsid assembly by using peptide-nanoparticles and the development of novel therapeutics
COVID-19 is a highly transmittable and pathogenic viral infection caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has emerged as a critical threat to global public health and the economy. From a pathological and biochemical point of view, the uninterrupted formation of the key viral proteins represents one of the most essential steps responsible for infection and pathogenesis of SARS-CoV-2. The replication cycle of SARS-CoV-2 in the host cells is marked with highly synchronized processes of protein expression, protein folding and nuclear capsid assembly that lead to the formation of new virus particles.
Hence, the disruption of viral protein homeostasis would represent a potential therapeutic strategy against SARS-CoV-2. Our initial study has suggested that the proteome of SARS-CoV-2 consists of numerous (≈70) hot spots (i.e., short hydrophobic sequence stretches with high aggregation propensity) that can be specifically targeted, to disrupt the viral protein homeostasis, by using specifically designed peptides. These peptides would be viral protein-specific and hence would not be able to interfere with the physiology of normal host cells. The peptides would favorably interact with the viral proteins, scrambled them and prevent their folding into the native functional state that would lead to the formation of protein aggregates, which would be cleared by proteasomal degradation of the host cells. The successful implementation of this approach would establish a novel and potential therapeutic strategy against COVID-19.
Researchers: Dr. Jay Kant Yadav (CURaj), Dr. Suman Tapryal (CURaj) Dr. Manish Singh (INST Mohali), Prof. Bhubaneshwar Mandal (IIT Guwahati).
