In silico strategies to identify protein-protein interaction modulator in cell-to-cell transmission of SARS CoV2.

RNA sequence data from SARS CoV2 patients helps to construct a gene network related to this disease. A detailed analysis of the human host response to SARS CoV2 with expression profiling by high-throughput sequencing has been accomplished with primary human lung epithelial cell lines. Using this data, the clustered gene annotation and gene network construction are performed with the help of the String database. Among the four clusters identified, only 1 with 44 genes could be annotated. Interestingly, this corresponded to basal cells with p = 1.37e - 05, which is relevant for respiratory tract infection. Functional enrichment analysis of genes present in the gene network has been completed using the String database and the Network Analyst tool. Among three types of cell-cell communication, only the anchoring junction between the basal cell membrane and the basal lamina in the host cell is involved in the virus transmission. In this junction point, a hemidesmosome structure plays a vital role in virus spread from one cell to basal lamina in the respiratory tract. In this protein complex structure, different integrin protein molecules of the host cell are used to promote the spread of virus infection into the extracellular matrix. So, small molecular blockers of different anchoring junction proteins, such as integrin alpha 3, integrin beta 1, can provide efficient protection against this deadly viral disease. ORF8 from SARS CoV2 virus can interact with both integrin proteins of human host. By using molecular docking technique, a ternary complex of these three proteins is modelled. Several oligopeptides are predicted as modulators for this ternary complex. In silico analysis of these modulators is very important to develop novel therapeutics for the treatment of SARS CoV2.

Passenger Surveillance Using Deep Learning in Post-COVID-19 Intelligent Transportation System.

Intelligent Transport System should be renovated in many aspects in post-pandemic situation like COVID-19. The passenger-count inside a car will be restricted based on the vehicle capacity and the COVID-19 hot-spot zone. Traffic rules will be impacted to align with a similar contagious outbreak. The on-road 'Yellow-Vulture' cameras need to incorporate such surveillance rules to monitor related anomalies for preventing contamination. To maintain safe-distance, an automatic surveillance system will be preferred by the Government very soon. Moreover, facial mask usage during the journey has become an essential habit to stop the spread of the infection. In this article, we have proposed a deep-Learning based framework that employs an augmented image data set to provide proper surveillance in the transport system to maintain the health protocols. Fast and accurate detection of the number of passengers inside a car and their face masks from the traffic inspection camera feed has been demonstrated. We have exploited the advantages of the popular Transfer Learning approach with novel variations of images while performing the training. To the best of our knowledge, this is the first attempt to watch over in-vehicle social-distancing in post-pandemic circumstances through deep-Learning based image analysis. The superiority of the proposed framework has been established over several state-of-the-art techniques using different numerical metrics and visual comparisons along with a support of statistical hypothesis test. Our technique has achieved 98.5 % testing accuracy in various adverse conditions. Zero-shot evaluation has been explored for the Real-Time-Medical-Mask-Detection data set Wang et al. (Real-Time-Medical-Mask-Detection, 2020a https://github.com/TheSSJ2612/Real-Time-Medical-Mask-Detection/, Accessed 14 Nov 2020), where we have attained 96.4 % accuracy that manifests the generalization of the network.

Time-Series Prediction for the Epidemic Trends of COVID-19 Using Conditional Generative Adversarial Networks Regression on Country-Wise Case Studies.

Probabilistic Regression is a statistical technique and a crucial problem in the machine learning domain which employs a set of machine learning methods to forecast a continuous target variable based on the value of one or multiple predictor variables. COVID-19 is a virulent virus that has brought the whole world to a standstill. The potential of the virus to cause inter human transmission makes the world a dangerous place. This article predicts the upcoming circumstances of the Corona virus to subside its action. We have performed Conditional GAN regression to anticipate the subsequent COVID-19 cases of five countries. The GAN variant CGAN is used to design the model and predict the COVID-19 cases for 3 months ahead with least error for the dataset provided. Each country is examined individually, due to their variation in population size, tradition, medical management and preventive measures. The analysis is based on confirmed data, as provided by the World Health Organization. This paper investigates how conditional Generative Adversarial Networks (GANs) can be used to accurately exhibit intricate conditional distributions. GANs have got spectacular achievement in producing convoluted high-dimensional data, but work done on their use for regression problems is minimal. This paper exhibits how conditional GANs can be employed in probabilistic regression. It is shown that conditional GANs can be used to evaluate a wide range of various distributions and be competitive with existing probabilistic regression models.

A network biology approach to identify crucial host targets for COVID-19.

The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.

Dense Dilated Deep Multiscale Supervised U-Network for biomedical image segmentation.

Biomedical image segmentation is essential for computerized medical image analysis. Deep learning algorithms allow us to design state-of-the-art models for solving segmentation problems. The U-Net and its variants have provided positive results across various datasets. However, the existing networks have the same receptive field at each level and the models are supervised only at the shallow level. Considering these two ideas, we have proposed the D3MSU-Net where the field of view in each level is varied depending upon the depth of the resolution layer and the model is supervised at each resolution level. We have evaluated our network in eight benchmark datasets such as Electron Microscopy, Lung segmentation, Montgomery Chest X-ray, Covid-Radiopaedia, Wound, Medetec, Brain MRI, and Covid-19 lung CT dataset. Additionally, we have provided the performance for various ablations. The experimental results show the superiority of the proposed network. The proposed D3MSU-Net and ablation models are available at www.github.com/shirshabose/D3MSUNET.

Strategies for COVID-19 Epidemiological Surveillance in India: Overall Policies Till June 2021.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has gripped the entire world, almost paralysing the human race in its entirety. The virus rapidly transmits via human-to-human medium resulting in a massive increase of patients with COVID-19. In order to curb the spread of the disease, an immediate action of complete lockdown was implemented across the globe. India with a population of over 1.3 billion was not an exception and took the challenge to execute phase-wise lockdown, unlock and partial lockdown activities. In this study, we intend to summarise these different phases that the Government of India (GoI) imposed to fight against SARS-CoV-2 so that it can act as a reference guideline to help controlling future waves of COVID-19 and similar pandemic situations in India.

Unveiling COVID-19-associated organ-specific cell types and cell-specific pathway cascade.

The novel coronavirus or COVID-19 has first been found in Wuhan, China, and became pandemic. Angiotensin-converting enzyme 2 (ACE2) plays a key role in the host cells as a receptor of Spike-I Glycoprotein of COVID-19 which causes final infection. ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells. In this study, the single-cell RNAseq data of the five tissues from different humans are curated and cell types with high expressions of ACE2 are identified. Subsequently, the protein-protein interaction networks have been established. From the network, potential biomarkers which can form functional hubs, are selected based on k-means network clustering. It is observed that angiotensin PPAR family proteins show important roles in the functional hubs. To understand the functions of the potential markers, corresponding pathways have been researched thoroughly through the pathway semantic networks. Subsequently, the pathways have been ranked according to their influence and dependency in the network using PageRank algorithm. The outcomes show some important facts in terms of infection. Firstly, renin-angiotensin system and PPAR signaling pathway can play a vital role for enhancing the infection after its intrusion through ACE2. Next, pathway networks consist of few basic metabolic and influential pathways, e.g. insulin resistance. This information corroborate the fact that diabetic patients are more vulnerable to COVID-19 infection. Interestingly, the key regulators of the aforementioned pathways are angiontensin and PPAR family proteins. Hence, angiotensin and PPAR family proteins can be considered as possible therapeutic targets. Contact: sagnik.sen2008@gmail.com, umaulik@cse.jdvu.ac.in Supplementary information: Supplementary data are available online.

Understanding structural malleability of the SARS-CoV-2 proteins and relation to the comorbidities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of the coronavirus disease (COVID-19), is a part of the $\beta $-Coronaviridae family. The virus contains five major protein classes viz., four structural proteins [nucleocapsid (N), membrane (M), envelop (E) and spike glycoprotein (S)] and replicase polyproteins (R), synthesized as two polyproteins (ORF1a and ORF1ab). Due to the severity of the pandemic, most of the SARS-CoV-2-related research are focused on finding therapeutic solutions. However, studies on the sequences and structure space throughout the evolutionary time frame of viral proteins are limited. Besides, the structural malleability of viral proteins can be directly or indirectly associated with the dysfunctionality of the host cell proteins. This dysfunctionality may lead to comorbidities during the infection and may continue at the post-infection stage. In this regard, we conduct the evolutionary sequence-structure analysis of the viral proteins to evaluate their malleability. Subsequently, intrinsic disorder propensities of these viral proteins have been studied to confirm that the short intrinsically disordered regions play an important role in enhancing the likelihood of the host proteins interacting with the viral proteins. These interactions may result in molecular dysfunctionality, finally leading to different diseases. Based on the host cell proteins, the diseases are divided in two distinct classes: (i) proteins, directly associated with the set of diseases while showing similar activities, and (ii) cytokine storm-mediated pro-inflammation (e.g. acute respiratory distress syndrome, malignancies) and neuroinflammation (e.g. neurodegenerative and neuropsychiatric diseases). Finally, the study unveils that males and postmenopausal females can be more vulnerable to SARS-CoV-2 infection due to the androgen-mediated protein transmembrane serine protease 2.

Topological Analysis for Sequence Variability: Case Study on more than 2K SARS-CoV-2 sequences of COVID-19 infected 54 countries in comparison with SARS-CoV-1 and MERS-CoV.

The pandemic due to novel coronavirus, SARS-CoV-2 is a serious global concern now. More than thousand new COVID-19 infections are getting reported daily for this virus across the globe. Thus, the medical research communities are trying to find the remedy to restrict the spreading of this virus, while the vaccine development work is still under research in parallel. In such critical situation, not only the medical research community, but also the scientists in different fields like microbiology, pharmacy, bioinformatics and data science are also sharing effort to accelerate the process of vaccine development, virus prediction, forecasting the transmissible probability and reproduction cases of virus for social awareness. With the similar context, in this article, we have studied sequence variability of the virus primarily focusing on three aspects: (a) sequence variability among SARS-CoV-1, MERS-CoV and SARS-CoV-2 in human host, which are in the same coronavirus family, (b) sequence variability of SARS-CoV-2 in human host for 54 different countries and (c) sequence variability between coronavirus family and country specific SARS-CoV-2 sequences in human host. For this purpose, as a case study, we have performed topological analysis of 2391 global genomic sequences of SARS-CoV-2 in association with SARS-CoV-1 and MERS-CoV using an integrated semi-alignment based computational technique. The results of the semi-alignment based technique are experimentally and statistically found similar to alignment based technique and computationally faster. Moreover, the outcome of this analysis can help to identify the nations with homogeneous SARS-CoV-2 sequences, so that same vaccine can be applied to their heterogeneous human population.

Molecular docking study of potential phytochemicals and their effects on the complex of SARS-CoV2 spike protein and human ACE2.

Angiotensin converting enzyme 2 (ACE2) (EC:3.4.17.23) is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). Since no specific medication is available to treat COVID-19, designing of new drug is important and essential. In this regard, in silico method plays an important role, as it is rapid and cost effective compared to the trial and error methods using experimental studies. Natural products are safe and easily available to treat coronavirus affected patients, in the present alarming situation. In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. Their molecular binding sites on spike protein bound structure with its receptor have been analyzed. From this analysis, hesperidin, emodin and chrysin are selected as competent natural products from both Indian and Chinese medicinal plants, to treat COVID-19. Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. This compound modulates the binding energy of bound structure of ACE2 and spike protein. This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable. As a result, this natural product can impart antiviral activity in SARS CoV2 infection. The antiviral activity of these five natural compounds are further experimentally validated with QSAR study.