Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community's massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155020PMC
http://dx.doi.org/10.1038/s41598-021-90296-2DOI Listing

Publication Analysis

Top Keywords

drug repurposing
16
repurposing candidates
12
rational selection
8
selection drug
8
drug
5
method rational
4
repurposing
4
candidates multimodal
4
multimodal knowledge
4
knowledge harmonization
4

Similar Publications

Protein kinases are central regulators of cell signaling and play pivotal roles in a wide array of diseases, most notably cancer and autoimmune disorders. The clinical success of kinase inhibitors-such as imatinib and osimertinib-has firmly established kinases as valuable drug targets. However, the development of selective, potent inhibitors remains challenging due to the conserved nature of the ATP-binding site, off-target effects, resistance mutations, and patient-specific variability.

View Article and Find Full Text PDF

Personalized treatment selection is crucial for cancer patients due to the high variability in drug response. While actionable mutations can increasingly inform treatment decisions, most therapies still rely on population-based approaches. Here, we introduce neural interaction explainable AI (NeurixAI), an explainable and highly scalable deep learning framework that models drug-gene interactions and identifies transcriptomic patterns linked with drug response.

View Article and Find Full Text PDF

Background: Acute and long-term mental health disorders correlate with coronavirus disease 2019 (COVID-19). The underlying mechanisms responsible for the coexistence of COVID-19 and depression remain unclear, and more research is needed to find hub genes and effective therapies. The main objective of this study was to evaluate gene-expression profiles and, identify key genes, and discovery potential therapeutic agents for co-occurrence in COVID-19 and major depressive disorder (MDD).

View Article and Find Full Text PDF

Pyrimethamine Inhibits Human Ovarian Cancer by Triggering Lethal Mitophagy via Activating the p38/JNK/ERK Pathway.

Oncol Res

September 2025

Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, 610041, China.

Objectives: Ovarian cancer, a leading cause of gynecological malignancy-related mortality, is characterized by limited therapeutic options and a poor prognosis. Although pyrimethamine has emerged as a promising candidate demonstrating efficacy in treating various tumors, the precise mechanisms of its antitumor effects remain obscure. This study was specifically designed to investigate the mode of action underlying the antitumor effects of pyrimethamine in preclinical settings.

View Article and Find Full Text PDF

There is a need to improve the discovery of new drugs for neglected tropical diseases (NTDs), as the lack of financial incentives has slowed their development. Currently, ivermectin and moxidectin are used in the management of onchocerciasis. We present a proof-of-concept study based on computational methods to find anti-infectives that can be repurposed or serve as lead compounds for onchocerciasis.

View Article and Find Full Text PDF