RESUMO

Monkeypox (MPXV) is one of the infectious viruses which caused morbidity and mortality problems in these years. Despite its danger to public health, there is no approved drug to stand and handle MPXV. On the other hand, drug repurposing is a promising screening method for the low-cost introduction of approved drugs for emerging diseases and viruses which utilizes computational methods. Therefore, drug repurposing is a promising approach to suggesting approved drugs for the MPXV. This paper proposes a computational framework for MPXV antiviral prediction. To do this, we have generated a new virus-antiviral dataset. Moreover, we applied several machine learning and one deep learning method for virus-antiviral prediction. The suggested drugs by the learning methods have been investigated using docking studies. The target protein structure is modeled using homology modeling and, then, refined and validated. To the best of our knowledge, this work is the first work to study deep learning methods for the prediction of MPXV antivirals. The screening results confirm that Tilorone, Valacyclovir, Ribavirin, Favipiravir, and Baloxavir marboxil are effective drugs for MPXV treatment.

Assuntos

RESUMO

Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature.

Assuntos

RESUMO

Efficient drug discovery relies on drug repurposing, an important and open research field. This work presents a novel factorization method and a practical comparison of different approaches for drug repurposing. First, we propose a novel tensor-matrix-tensor (TMT) formulation as a new data array method with a gradient-based factorization procedure. Additionally, this paper examines and contrasts four computational drug repurposing approaches-factorization-based methods, machine learning methods, deep learning methods, and graph neural networks-to fulfill the second purpose. We test the strategies on two datasets and assess each approach's performance, drawbacks, problems, and benefits based on results. The results demonstrate that deep learning techniques work better than other strategies and that their results might be more reliable. Ultimately, graph neural methods need to be in an inductive manner to have a reliable prediction.

RESUMO

Drug repurposing is an active area of research that aims to decrease the cost and time of drug development. Most of those efforts are primarily concerned with the prediction of drug-target interactions. Many evaluation models, from matrix factorization to more cutting-edge deep neural networks, have come to the scene to identify such relations. Some predictive models are devoted to the prediction's quality, and others are devoted to the efficiency of the predictive models, e.g., embedding generation. In this work, we propose new representations of drugs and targets useful for more prediction and analysis. Using these representations, we propose two inductive, deep network models of IEDTI and DEDTI for drug-target interaction prediction. Both of them use the accumulation of new representations. The IEDTI takes advantage of triplet and maps the input accumulated similarity features into meaningful embedding corresponding vectors. Then, it applies a deep predictive model to each drug-target pair to evaluate their interaction. The DEDTI directly uses the accumulated similarity feature vectors of drugs and targets and applies a predictive model on each pair to identify their interactions. We have done a comprehensive simulation on the DTINet dataset as well as gold standard datasets, and the results show that DEDTI outperforms IEDTI and the state-of-the-art models. In addition, we conduct a docking study on new predicted interactions between two drug-target pairs, and the results confirm acceptable drug-target binding affinity between both predicted pairs.

Assuntos

RESUMO

BACKGROUND: Due to the high resource consumption of introducing a new drug, drug repurposing plays an essential role in drug discovery. To do this, researchers examine the current drug-target interaction (DTI) to predict new interactions for the approved drugs. Matrix factorization methods have much attention and utilization in DTIs. However, they suffer from some drawbacks. METHODS: We explain why matrix factorization is not the best for DTI prediction. Then, we propose a deep learning model (DRaW) to predict DTIs without having input data leakage. We compare our model with several matrix factorization methods and a deep model on three COVID-19 datasets. In addition, to ensure the validation of DRaW, we evaluate it on benchmark datasets. Furthermore, as an external validation, we conduct a docking study on the COVID-19 recommended drugs. RESULTS: In all cases, the results confirm that DRaW outperforms matrix factorization and deep models. The docking results approve the top-ranked recommended drugs for COVID-19. CONCLUSIONS: In this paper, we show that it may not be the best choice to use matrix factorization in the DTI prediction. Matrix factorization methods suffer from some intrinsic issues, e.g., sparsity in the domain of bioinformatics applications and fixed-unchanged size of the matrix-related paradigm. Therefore, we propose an alternative method (DRaW) that uses feature vectors rather than matrix factorization and demonstrates better performance than other famous methods on three COVID-19 and four benchmark datasets.

Assuntos