Tivozanib for COVID-19

Abstract Background Viruses such as Ebola, Marburg, influenza, mpox, MERS-CoV, SARS-CoV, and SARS-CoV-2 pose a significant risk for future pandemics. Developing novel antiviral medicines can be time-consuming and resource intensive. Repurposing existing medicines with antiviral activity offers a faster, cost-effective strategy to expand treatment options during public health emergencies. This scan aimed to identify and synthesise recent evidence on repurposed antiviral medicines under investigation for these viruses. Method A horizon scanning approach was employed, starting with a targeted search in Embase, followed by a systematic search of ClinicalTrials.gov to capture the developmental stages of the technologies. Eligible technologies included UK- or EU-licensed medicines repurposed as antiviral therapies for the viruses of interest. Vaccines, unlicensed medicines, and already approved treatments for the targeted viruses were excluded. Results A total of 196 repurposed technologies targeting the viruses were identified from published literature, and the expanded search on the clinical trials registry yielded 58 technologies in active clinical development. Interventional clinical trial activity was limited to influenza and COVID-19, with 29 technologies for COVID-19 and two for influenza advancing to phase III evaluation. For other viruses, proposed antiviral candidates were identified in the literature but had not progressed into clinical development. Commonly investigated pharmacological classes included direct-acting antivirals, tyrosine kinase inhibitors, immunomodulators, and anti-inflammatory agents. Conclusion Repurposing antiviral medicines represents a pragmatic strategy for rapid therapeutic deployment against emerging viral threats. Collaboration among researchers, policymakers, research funders, and regulatory bodies will be essential to improve pandemic preparedness and support repurposing efforts in emergency situations.

Background: The COVID-19 pandemic caused by SARS-CoV-2 is an unparalleled health risk, needing fast antiviral medication development. One of the most effective strategies for developing therapies against novel and emerging viruses is drug repurposing. Recently, systems biology approaches toward the discovery of repurposing medications are gaining prominence. Aim: This study aimed to implement a systems biology approach to identify crucial drug targets as well as potential drug candidates against COVID infection. Methods: Our approach utilizes differential gene expression in COVID conditions that enable the construction of a protein-protein interaction (PPI) network. Core clusters were extracted from this network, followed by molecular enrichment analysis. This process identified critical drug targets and potential drug candidates targeting various stages of COVID-19 infection. Results: The network was built using the top 200 differently expressed genes in mild, moderate, and severe COVID-19 infections. Top 3 clusters for each disease condition were identified, representing the core mechanism of the network. Molecular enrichment revealed the majority of the pathways in the mild state were associated with transcription regulation, protein folding, angiogenesis, and cytokine-signaling pathways. Whereas, the enriched pathways in moderate and severe disease states were predominately linked with the immune system and apoptotic processes, which include NF-kappaB signaling, cytokine signaling, TNF-mediated signaling, and oxidative stress-induced cell death. Further analysis identifies 28 potential drugs that can be repurposed to treat moderate and severe COVID-19, most of which are currently used in cancer treatment. Conclusion: Interestingly, some of the proposed drugs have demonstrated inhibitory effects against SARS-CoV-2, as supported by literature evidence. Overall, the drug repurposing method described here will help develop potential antiviral medications to treat emerging COVID strains.