Acute eosinophilic pneumonia-like syndrome post-initiation of vortioxetine.

A man in his mid-30s presented to the emergency department with a 1-week history of fatigue, loss of appetite, fever and productive (yellow) cough. This progressed to requiring admission to intensive care needing a oxygen therapy via high-flow nasal cannula for acute hypoxaemic respiratory failure. He had recently started vortioxetine for major depressive disorder, and his acute symptoms correlated with an increase in the dose of vortioxetine. For more than 20 years, rare but consistent reports of serotonergic medications have been implicated in eosinophilic pulmonary conditions. During this same period, serotonergic medications have become a mainstay solution for a wide range of depressive symptoms and disorders. This is the first report of an eosinophilic pneumonia-like syndrome occurring while consuming the novel serotonergic medication vortioxetine.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.

Design, synthesis and docking study of Vortioxetine derivatives as a SARS-CoV-2 main protease inhibitor.

PURPOSE: Vortioxetine an anti-depressant FDA-drug recently reported showing better in vitro efficacy against SARS-CoV-2. METHODS: In this study, we have synthesized ten new derivatives having alkenes, alkynes, benzyl, aryl, and mixed carbamate at the N-terminal of vortioxetine. Then the binding energy and interactions with the crucial amino acid residues in the binding pocket of main protease (Mpro) of SARS-CoV-2, of reported and ten newly synthesized vortioxetine derivatives (total thirty-one) in comparison with remdesivir are analyzed and presented in this paper. RESULTS: Based on the docking scores predicted by ADV and AD, most vortioxetine derivatives showed better binding efficiency towards Mpro of SARS-CoV-2 in comparison with remdesivir (an EUA approved drug against SARS-CoV-2 Mpro) and vortioxetine. CONCLUSION: This study shows that some vortioxetine derivatives can be developed into promising drugs for COVID-19 treatment.

Jumping from Fragment to Drug via Smart Scaffolds.

A focused drug repurposing approach is described where an FDA-approved drug is rationally selected for biological testing based on structural similarities to a fragment compound found to bind a target protein by an NMR screen. The approach is demonstrated by first screening a curated fragment library using 19 F NMR to discover a quality binder to ACE2, the human receptor required for entry and infection by the SARS-CoV-2 virus. Based on this binder, a highly related scaffold was derived and used as a "smart scaffold" or template in a computer-aided finger-print search of a library of FDA-approved or marketed drugs. The most interesting structural match involved the drug vortioxetine which was then experimentally shown by NMR spectroscopy to bind directly to human ACE2. Also, an ELISA assay showed that the drug inhibits the interaction of human ACE2 to the SARS-CoV-2 receptor-binding-domain (RBD). Moreover, our cell-culture infectivity assay confirmed that vortioxetine is active against SARS-CoV-2 and inhibits viral replication. Thus, the use of "smart scaffolds" based on binders from fragment screens may have general utility for identifying candidates of FDA-approved or marketed drugs as a rapid repurposing strategy. Similar approaches can be envisioned for other fields involving small-molecule chemical applications.

Identification of Potent and Safe Antiviral Therapeutic Candidates Against SARS-CoV-2.

COVID-19 pandemic has infected millions of people with mortality exceeding >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 >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.