Monensin for COVID-19
Monensin has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2, Frontiers in Immunology, doi:10.3389/fimmu.2020.586572 ,
COVID-19 pandemic has infected millions of people with mortality exceeding &gt;1 million. There is an urgent need to find therapeutic agents that can help clear the virus to prevent severe disease and death. Identifying effective and safer drugs can provide more options to treat COVID-19 infections either alone or in combination. Here, we performed a high throughput screening of approximately 1,700 US FDA-approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 20 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine besylate, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, mefloquine, and thioridazine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of &gt;600, indicating a wide therapeutic window compared to hydroxychloroquine which had a safety index of 22 in similar experiments. Mechanistically, five of the effective compounds (fendiline HCl, monensin sodium salt, vortioxetine, sertraline HCl, and salifungin) were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA-approved compounds can provide much needed therapeutic options that we urgently need during the midst of the pandemic.
Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection, Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2021579118 ,
Significance COVID-19 is a global pandemic currently lacking an effective cure. We used a cell-based infection assay to screen more than 3,000 agents used in humans and animals and identified 15 with antiinfective activity, ranging from 0.1 nM to 50 μM. We then used in vitro enzymatic assays combined with computer modeling to confirm the activity of those against the viral protease and RNA polymerase. In addition, several herbal medicines were found active in the cell-based infection assay. To further evaluate the efficacy of these promising compounds in animal models, we developed a challenge assay with hamsters and found that mefloquine, nelfinavir, and extracts of Ganoderma lucidum (RF3), Perilla frutescens , and Mentha haplocalyx were effective against SARS-CoV-2 infection.
Anticancer pan-ErbB inhibitors reduce inflammation and tissue injury and exert broad-spectrum antiviral effects, bioRxiv, doi:10.1101/2021.05.15.444128 ,
AbstractTargeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, 2 and 4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, pro-inflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production and disruption of the blood-brain barrier integrity in microfluidic-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof-of-principle for a repurposed, ErbB-targeted approach to combat emerging viruses.
Analysis of transcriptomic responses to SARS-CoV-2 reveals plausible defective pathways responsible for increased susceptibility to infection and complications and helps to develop fast-track repositioning of drugs against COVID-19, Computers in Biology and Medicine, doi:10.1016/j.compbiomed.2022.106029 ,
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