Drug Repositioning for Coronavirus (COVID-19) using Different Deep Learning Architectures

In December 2019, the COVID-19 epidemic was found in Wuhan, China, and soon hundreds of millions were infected. Therefore, several efforts were made to identify commercially available drugs to repurpose them against COVID-19. Inferring potential drug indications through computational drug repositioning is an efficient method. The drug repositioning problem is a top-K recommendation function that presents the most likely drugs for specific diseases based on drug and disease-related data. The accurate prediction of drug-target interactions (DTI) is very important for drug repositioning. Deep learning (DL) models were recently exploited for promising DTI prediction performance. To build deep learning models for DTI prediction, encoder-decoder architectures can be utilized. In this paper, a deep learning-based drug repositioning approach is proposed, which is composed of two experimental phases. Firstly, training and evaluating different deep learning encoder-decoder architecture models using the benchmark DAVIS Dataset. The trained deep learning models have been evaluated using two evaluation metrics;mean square error and the concordance index. Secondly, predicting antiviral drugs for Covid-19 using the trained deep learning models created during the first phase. In this phase, these models have been experimented to predict different antiviral drug lists, which then have been compared with a recently published antiviral drug list for Covid-19 using the concordance index metric. The overall experimental results of both phases showed that the most accurate three deep learning compound-encoder/protein-encoder architectures are Morgan/AAC, CNN/AAC, and CNN/CNN with best values for the mean square error, the first phase concordance index, and the second phase concordance index. © 2023,International Journal of Advanced Computer Science and Applications. All Rights Reserved.

CNN-OSBO Encoder-Decoder Architecture for Drug-Target Interaction (DTI) Prediction of Covid-19 Targets

Drug Target Interaction (DTI) prediction is an important factor is drug discovery and repositioning (DDR) since it detects the response of a drug over a target protein. The Coronavirus disease 2019 (COVID-19) disease created groups of deadly pneumonia with clinical appearance mostly similar to SARS-CoV. The precise diagnosis of COVID-19 clinical outcome is more challenging, since the diseases has various forms with varying structures. So predicting the interactions between various drugs with the SARS-CoV target protein is very crucial need in these days, which may leads to discovery of new drugs for the deadly disease. Recently, Deep learning (DL) techniques have been applied by the researches for DTI prediction. Since CNN is one of the major DL models which has the ability to create predictive feature vectors or embeddings, CNN-OSBO encoder-decoder architecture for DTI prediction of Covid-19 targets has been designed Given the input drug and Covid-19 target pair of data, they are fed into the Convolution Neural Networks (CNN) with Opposition based Satin Bowerbird Optimizer (OSBO) encoder modules, separately. Here OSBO is utilized for regulating the hyper parameters (HPs) of CNN layers. Both the encoded data are then embedded to create a binding module. Finally the CNN Decoder module predicts the interaction of drugs over the Covid-19 targets by returning an affinity or interaction score. Experimental results state that DTI prediction using CNN+OSBO achieves better accuracy results when compared with the existing techniques. © 2022 IEEE.

Bioinformatics approaches for unveiling virus-host interactions.

The coronavirus disease-2019 (COVID-19) pandemic has elucidated major limitations in the capacity of medical and research institutions to appropriately manage emerging infectious diseases. We can improve our understanding of infectious diseases by unveiling virus-host interactions through host range prediction and protein-protein interaction prediction. Although many algorithms have been developed to predict virus-host interactions, numerous issues remain to be solved, and the entire network remains veiled. In this review, we comprehensively surveyed algorithms used to predict virus-host interactions. We also discuss the current challenges, such as dataset biases toward highly pathogenic viruses, and the potential solutions. The complete prediction of virus-host interactions remains difficult; however, bioinformatics can contribute to progress in research on infectious diseases and human health.

Towards De Novo Drug Design for the Coronavirus: A Drug-Target Interaction Prediction Approach using Atom-enhanced Graph Neural Network with Multi-hop Gating Mechanism

For humans, the COVID-19 pandemic and Coronavirus have undeniably been a nightmare. Although there are effective vaccines, specific drugs are still urgent. Normally, to identify potential drugs, one needs to design and then test interactions between the drug and the virus in an in silico manner for determining candidates. This Drug-Target Interaction (DTI) process, can be done by molecular docking, which is too complicated and time-consuming for manual works. Therefore, it opens room for applying Artificial Intelligence (AI) techniques. In particular, Graph Neural Network (GNN) attracts recent attention since its high suitability for the nature of drug compounds and virus proteins. However, to introduce such a representation well-reflecting biological structures of biological compounds is not a trivial task. Moreover, since available datasets of Coronavirus are still not highly popular, the recently developed GNNs have been suffering from overfitting on them. We then address those issues by proposing a novel model known as Atom-enhanced Graph Neural Network with Multi-hop Gating Mechanism. On one hand, our model can learn more precise features of compounds and proteins. On the other hand, we introduce a new gating mechanism to create better atom representation from non-neighbor information. Once applying transfer learning from very large databanks, our model enjoys promising performance, especially when experimenting with Coronavirus. © 2022 IEEE.

Discovering missing edges in drug-protein networks: Repurposing drugs for SARS-CoV-2

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, led to a global health crisis, with more than 157 million cases confirmed infected by May 2021. Effective medication is desperately needed. Predicting drug-target interaction (DTI) is an important step to discover novel uses of chemical structures. Here, we develop a pipeline to predict novel DTIs based on the proteins of the coronavirus. Different datasets (human/SARSCoV-2 Protein-Protein interaction (PPI), Drug-Drug similarity (DD sim), and DTIs) are used and combined. After mapping all datasets onto a heterogeneous graph, path-related features are extracted. We then applied various machine learning (ML) algorithms to model our dataset and predict novel DTIs among unlabeled pairs. Possible drugs identified by the models with a high frequency are reported. In addition, evidence of the efficiency of the predicted medicines by the models against COVID-19 are presented. The proposed model can then be generalized to contain other features that provide a context to predict medicine for different diseases. © 2021 IEEE.

Discovering DTI and DDI by Knowledge Graph with MHRW and Improved Neural Network

Drug discovery is of great significance in medical and biological research, while the study of Drug-Target Interaction (DTI) and Drug-Drug Interaction (DDI) can help accelerate drug discovery progress. This paper proposes a new hybrid method for DTI prediction and DDI prediction, which is called MHRW2Vec-TBAN that combines graph representation learning and neural network. MHRW2VecTBAN first constructs knowledge graph KG-DTI and KG-DDI that integrate data related to drugs and targets. Then, an improved graph representation learning model, MHRW2Vec model, is used to obtain feature vectors of reflecting the network structure information for improving the performance of representation learning. Finally, the feature vectors obtained are input to the improved neural network model TextCNN-BiLSTM-Attention Network (TBAN). The experimental results show that, compared with other existing methods, our method could discover more deeper the relationship between drugs and their potential neighborhoods, and has great improvements in DTI prediction and DDI prediction. In addition, the case study of prediction COVID-19 DTI also shows that the proposed model has the potential for actual drug discovery. © 2021 IEEE.

PEPPI: Whole-proteome Protein-protein Interaction Prediction through Structure and Sequence Similarity, Functional Association, and Machine Learning.

Proteome-wide identification of protein-protein interactions is a formidable task which has yet to be sufficiently addressed by experimental methodologies. Many computational methods have been developed to predict proteome-wide interaction networks, but few leverage both the sensitivity of structural information and the wide availability of sequence data. We present PEPPI, a pipeline which integrates structural similarity, sequence similarity, functional association data, and machine learning-based classification through a naïve Bayesian classifier model to accurately predict protein-protein interactions at a proteomic scale. Through benchmarking against a set of 798 ground truth interactions and an equal number of non-interactions, we have found that PEPPI attains 4.5% higher AUROC than the best of other state-of-the-art methods. As a proteomic-scale application, PEPPI was applied to model the interactions which occur between SARS-CoV-2 and human host cells during coronavirus infection, where 403 high-confidence interactions were identified with predictions covering 73% of a gold standard dataset from PSICQUIC and demonstrating significant complementarity with the most recent high-throughput experiments. PEPPI is available both as a webserver and in a standalone version and should be a powerful and generally applicable tool for computational screening of protein-protein interactions.

Incorporating FPConv-DTI deep learning network and borderline-SMOTE algorithm for predicting drug-target interactions

Drug-target interactions prediction is of great significance in medical and biological research, but traditional laboratory methods have disadvantages such as high cost and time-consuming. Therefore, in recent years, deep learning, similarity calculation methods and other methods are becoming more and more widely applied to related research. This paper proposes an improved deep learning model, named as FPConv-DTI, which uses the fingerprint information of drug and the evolution feature information of protein based on a convolutional neural network. The Borderline-SMOTE algorithm is also used to generate new positive examples for training to solve the imbalance problem, and combines the number of sample data to process the input differently. Experiments have been carried out with four standard datasets and Drugbank dataset. The results show that compared with other methods, our method has greatly improvement for predicting drug-target interactions. In addition, some COVID-19 drugs are also predicted with the best-performing model, which shows that FPConv-DTI model is the potential for practical drug prediction. © 2021 Association for Computing Machinery.

Multi-schema computational prediction of the comprehensive SARS-CoV-2 vs. human interactome.

BACKGROUND: Understanding the disease pathogenesis of the novel coronavirus, denoted SARS-CoV-2, is critical to the development of anti-SARS-CoV-2 therapeutics. The global propagation of the viral disease, denoted COVID-19 ("coronavirus disease 2019"), has unified the scientific community in searching for possible inhibitory small molecules or polypeptides. A holistic understanding of the SARS-CoV-2 vs. human inter-species interactome promises to identify putative protein-protein interactions (PPI) that may be considered targets for the development of inhibitory therapeutics. METHODS: We leverage two state-of-the-art, sequence-based PPI predictors (PIPE4 & SPRINT) capable of generating the comprehensive SARS-CoV-2 vs. human interactome, comprising approximately 285,000 pairwise predictions. Three prediction schemas (all, proximal, RP-PPI) are leveraged to obtain our highest-confidence subset of PPIs and human proteins predicted to interact with each of the 14 SARS-CoV-2 proteins considered in this study. Notably, the use of the Reciprocal Perspective (RP) framework demonstrates improved predictive performance in multiple cross-validation experiments. RESULTS: The all schema identified 279 high-confidence putative interactions involving 225 human proteins, the proximal schema identified 129 high-confidence putative interactions involving 126 human proteins, and the RP-PPI schema identified 539 high-confidence putative interactions involving 494 human proteins. The intersection of the three sets of predictions comprise the seven highest-confidence PPIs. Notably, the Spike-ACE2 interaction was the highest ranked for both the PIPE4 and SPRINT predictors with the all and proximal schemas, corroborating existing evidence for this PPI. Several other predicted PPIs are biologically relevant within the context of the original SARS-CoV virus. Furthermore, the PIPE-Sites algorithm was used to identify the putative subsequence that might mediate each interaction and thereby inform the design of inhibitory polypeptides intended to disrupt the corresponding host-pathogen interactions. CONCLUSION: We publicly released the comprehensive sets of PPI predictions and their corresponding PIPE-Sites landscapes in the following DataVerse repository: https://www.doi.org/10.5683/SP2/JZ77XA. The information provided represents theoretical modeling only and caution should be exercised in its use. It is intended as a resource for the scientific community at large in furthering our understanding of SARS-CoV-2.

Network-based virus-host interaction prediction with application to SARS-CoV-2.

COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has quickly become a global health crisis since the first report of infection in December of 2019. However, the infection spectrum of SARS-CoV-2 and its comprehensive protein-level interactions with hosts remain unclear. There is a massive amount of underutilized data and knowledge about RNA viruses highly relevant to SARS-CoV-2 and proteins of their hosts. More in-depth and more comprehensive analyses of that knowledge and data can shed new light on the molecular mechanisms underlying the COVID-19 pandemic and reveal potential risks. In this work, we constructed a multi-layer virus-host interaction network to incorporate these data and knowledge. We developed a machine-learning-based method to predict virus-host interactions at both protein and organism levels. Our approach revealed five potential infection targets of SARS-CoV-2 and 19 highly possible interactions between SARS-CoV-2 proteins and human proteins in the innate immune pathway.

SARS-CoV-2-human protein-protein interaction network.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus which caused the coronavirus disease 2019 pandemic and infected more than 12 million victims and resulted in over 560,000 deaths in 213 countries around the world. Having no symptoms in the first week of infection increases the rate of spreading the virus. The increasing rate of the number of infected individuals and its high mortality necessitates an immediate development of proper diagnostic methods and effective treatments. SARS-CoV-2, similar to other viruses, needs to interact with the host proteins to reach the host cells and replicate its genome. Consequently, virus-host protein-protein interaction (PPI) identification could be useful in predicting the behavior of the virus and the design of antiviral drugs. Identification of virus-host PPIs using experimental approaches are very time consuming and expensive. Computational approaches could be acceptable alternatives for many preliminary investigations. In this study, we developed a new method to predict SARS-CoV-2-human PPIs. Our model is a three-layer network in which the first layer contains the most similar Alphainfluenzavirus proteins to SARS-CoV-2 proteins. The second layer contains protein-protein interactions between Alphainfluenzavirus proteins and human proteins. The last layer reveals protein-protein interactions between SARS-CoV-2 proteins and human proteins by using the clustering coefficient network property on the first two layers. To further analyze the results of our prediction network, we investigated human proteins targeted by SARS-CoV-2 proteins and reported the most central human proteins in human PPI network. Moreover, differentially expressed genes of previous researches were investigated and PPIs of SARS-CoV-2-human network, the human proteins of which were related to upregulated genes, were reported.