The SARS-CoV-2 pandemic, declared as a global health emergency by the WHO in February 2020, has currently infected more than 6 million people with fatalities near 371,000 and increasing exponentially, in absence of vaccines and drugs. The pathogenesis of SARS-CoV-2 is still being elucidated. Identifying potential targets and repurposing drugs as therapeutic options is the need of the hour. In this review, we focus on potential druggable targets and suitable therapeutics, currently being explored in clinical trials, to treat SARS-CoV-2 infection. A brief understanding of the complex interactions of both viral as well as host targets, and the possible repurposed drug candidates are described with an emphasis on understanding the mechanisms at the molecular level.
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http://dx.doi.org/10.4155/fmc-2020-0147 | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
January 2025
MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Department of Bioinformatics and Computational Biology, School of Life Sciences, Suzhou Medical College of Soochow University, Suzhou 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou 215123, China; Key Laboratory of Alkene-carbon Fibres-based Technology & Application for Detection of Major Infectious Diseases, Soochow University, Suzhou 215123, China; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, China. Electronic address:
Cancer, a heterogeneous disease, presents significant challenges for drug development due to its complex etiology. Drug repurposing, particularly through network medicine approaches, offers a promising avenue for cancer treatment by analyzing how drugs influence cellular networks on a systemic scale. The advent of large-scale proteomics data provides new opportunities to elucidate regulatory mechanisms specific to cancer subtypes.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia.
As a promising candidate for tackling drug-resistant cancers, triptolide, a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, has been developed. This review summarizes potential antitumor activities, including the suppression of RNA polymerase II, the suppression of heat shock proteins (HSP70 and HSP90), and the blockade of NF-kB signalling. Triptolide is the first known compound to target cancer cells specifically but spare normal cells, and it has success in treating cancers that are difficult to treat, including pancreatic, breast, and lung cancers.
View Article and Find Full Text PDFViruses
January 2025
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome.
View Article and Find Full Text PDFViruses
January 2025
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.
View Article and Find Full Text PDFPharmaceuticals (Basel)
December 2024
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Aurora kinase B (AurB) is a pivotal regulator of mitosis, making it a compelling target for cancer therapy. Despite significant advances in protein kinase inhibitor development, there are currently no AurB inhibitors readily available for therapeutic use. This study introduces a machine learning-assisted drug repurposing framework integrating quantitative structure-activity relationship (QSAR) modeling, molecular fingerprints-based classification, molecular docking, and molecular dynamics (MD) simulations.
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