Fluticasone 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.

<ns4:p>We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL<ns4:sup>pro</ns4:sup>) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL<ns4:sup>pro</ns4:sup> molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.</ns4:p>

Background: COVID-19 is a critical pandemic that has affected human communities worldwide. Although it is urgent to rapidly develop effective drugs, large number of candidate drug compounds may be useful for treating COVID-19, and evaluation of these drugs is time-consuming and costly. Thus, screening to identify potentially effective drugs prior to experimental validation is necessary. Method: In this study, we applied the recently proposed method tensor decomposition (TD)-based unsupervised feature extraction (FE) to gene expression profiles of multiple lung cancer cell lines infected with severe acute respiratory syndrome coronavirus 2. We identified drug candidate compounds that significantly altered the expression of the 163 genes selected by TD-based unsupervised FE. Results: Numerous drugs were successfully screened, including many known antiviral drug compounds. Conclusions: The drugs screened using our strategy may be effective candidates for treating patients with COVID-19.