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In this study, the Nsp12-Nsp8 complex of SARS-CoV-2 was targeted with structure-based and computer-aided drug design approach because of its vital role in viral replication. Sequence analysis of RNA-dependent RNA polymerase (Nsp12) sequences from 30,366 different isolates were analysed for possible mutations. FDA-approved and investigational drugs were screened for interaction with both mutant and wild-type Nsp12-Nsp8 interfaces. Sequence analysis revealed that 70.42% of Nsp12 sequences showed conserved P323L mutation, located in the Nsp8 binding cleft. Compounds were screened for interface interaction, any with XP GScores lower than -7.0 kcal/mol were considered as possible interface inhibitors. RX-3117 (fluorocyclopentenyl cytosine) and Nebivolol had the highest binding affinities in both mutant and wild-type enzymes, therefore they were selected and resultant protein-ligand complexes were simulated for analysis of stability over 100 ns. Although the selected ligands had partial mobility in the binding cavity, they were not removed from the binding pocket after 100 ns. The ligand RX-3117 remained in the same position in the binding pocket of the mutant and wild-type enzyme after 100 ns MD simulation. However, the ligand Nebivolol folded and embedded in the binding pocket of mutant Nsp12 protein. Overall, FDA-approved and investigational drugs are able to bind to the Nsp12-Nsp8 interaction interface and prevent the formation of the Nsp12-Nsp8 complex. Interruption of viral replication by drugs proposed in this study should be further tested to pave the way for in vivo studies towards the treatment of COVID-19.Communicated by Ramaswamy H. Sarma.

A novel pathogen, named SARS-CoV-2, has caused an unprecedented worldwide pandemic in the first half of 2020. As the SARS-CoV-2 genome sequences have become available, one of the important focus of scientists has become tracking variations in the viral genome. In this study, 30366 SARS-CoV-2 isolate genomes were aligned using the software developed by our group (ODOTool) and 11 variations in SARS-CoV-2 genome over 10% of whole isolates were discussed. Results indicated that, frequency rates of these 11 variations change between 3.56%-88.44 % and these rates differ greatly depending on the continents they have been reported. Despite some variations being in low frequency rate in some continents, C14408T and A23403G variations on Nsp12 and S protein, respectively, observed to be the most prominent variations all over the world, in general, and both cause missense mutations. It is also notable that most of isolates carry C14408T and A23403 variations simultaneously and also nearly all isolates carrying the G25563T variation on ORF3a, also carry C14408T and A23403 variations, although their location distributions are not similar. All these data should be considered towards development of vaccine and antiviral treatment strategies as well as tracing diversity of virus in all over the world. [ABSTRACT FROM AUTHOR]

It has been reported that a deadly virus known as COVID-19 has arisen in China and has spread rapidly throughout the country. The globe was shattered, and a large number of people on the planet died. It quickly became an epidemic due to the absence of apparent symptoms and causes for patients, confusion appears due to the lack of sufficient laboratory results, and its intelligent algorithms were used to make decisions on clinical outcomes. This study developed a new framework for medical datasets with high missing values based on deep-learning optimization models. The robustness of our model is achieved by combining: Data Missing Care (DMC) Framework to overcome the problem of high missing data in medical datasets, and Grid-Search optimization used to develop an improved deep predictive training model for patients with COVID-19 by setting multiple hyperparameters and tuning assessments on three deep learning algorithms: ANN (Artificial Neural Network), CNN (Convolutional Neural Network), and Recurrent Neural Networks (RNN). The experiment results conducted on three medical datasets showed the effectiveness of our hybrid approach and an improvement in accuracy and efficiency since all the evaluation metrics were close to ideal for all deep learning classifiers. We got the best evaluation in terms of accuracy 98%, precession 98.5%, F1-score 98.6%, and ROC Curve (95% to 99%) for the COVID-19 dataset provided by GitHub. The second dataset is also Covid-19 provided by Albert Einstein Hospital with high missing data after applying our approach the accuracy reached more than 91%. Third dataset for Cervical Cancer provided by Kaggle all the evaluation metrics reached more than 95%. The proposed formula for processing this type of data can replace the traditional formats in optimization while providing high accuracy and less time to classify patients. Whereas, the experimental results of our approach, supported by comprehensive statistical analysis, can improve the overall evaluation performance of the problem of classifying medical data sets with high missing values. Therefore, this approach can be used in many areas such as energy management, environment, and medicine. [ABSTRACT FROM AUTHOR]

The coronavirus pandemic has affected people all over the world and posed a great challenge to international health systems. To aid early detection of coronavirus disease-2019 (COVID-19), this study proposes a real-time detection system based on the Internet of Things framework. The system collects real-time data from users to determine potential coronavirus cases, analyses treatment responses for people who have been treated, and accurately collects and analyses the datasets. Artificial intelligence-based algorithms are an alternative decision-making solution to extract valuable information from clinical data. This study develops a deep learning optimisation system that can work with imbalanced datasets to improve the classification of patients. A synthetic minority oversampling technique is applied to solve the problem of imbalance, and a recursive feature elimination algorithm is used to determine the most effective features. After data balance and extraction of features, the data are split into training and testing sets for validating all models. The experimental predictive results indicate good stability and compatibility of the models with the data, providing maximum accuracy of 98% and precision of 97%. Finally, the developed models are demonstrated to handle data bias and achieve high classification accuracy for patients with COVID-19. The findings of this study may be useful for healthcare organisations to properly prioritise assets. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 has caused COVID-19 outbreak with nearly 2 M infected people and over 100K death worldwide, until middle of April 2020. There is no confirmed drug for the treatment of COVID-19 yet. As the disease spread fast and threaten human life, repositioning of FDA approved drugs may provide fast options for treatment. In this aspect, structure-based drug design could be applied as a powerful approach in distinguishing the viral drug target regions from the host. Evaluation of variations in SARS-CoV-2 genome may ease finding specific drug targets in the viral genome. In this study, 3458 SARS-CoV-2 genome sequences isolated from all around the world were analyzed. Incidence of C17747T and A17858G mutations were observed to be much higher than others and they were on Nsp13, a vital enzyme of SARS-CoV-2. Effect of these mutations was evaluated on protein-drug interactions using in silico methods. The most potent drugs were found to interact with the key and neighbor residues of the active site responsible from ATP hydrolysis. As result, cangrelor, fludarabine, folic acid and polydatin were determined to be the most potent drugs which have potency to inhibit both the wild type and mutant SARS-CoV-2 helicase. Clinical data supporting these findings would be important towards overcoming COVID-19. • Two mutations (C17747T and A17858G) were determined in SARS-CoV-2 genomes. • Impact of these mutations on a vital enzyme Helicase of SARS-CoV-2 were analyzed using in silico approaches. • High-throughput virtual screening method was used to prioritize SARS-CoV-2 Nsp13 candidate inhibitors from FDA approved drugs. • Results showed that cangrelor, fludarabine, folic acid and polydatin were the most potent drugs interacted with structures. • Clinical data supporting these in silico findings would be of great importance. [ABSTRACT FROM AUTHOR]