Loratadine for COVID-19

Antihistamines have potent efficacy to alleviate COVID-19 (Coronavirus disease 2019) symptoms such as anti-inflammation and as a pain reliever. However, the pharmacological mechanism(s), key target(s), and drug(s) are not documented well against COVID-19. Thus, we investigated to decipher the most significant components and how its research methodology was utilized by network pharmacology. The list of 32 common antihistamines on the market were retrieved via drug browsing databases. The targets associated with the selected antihistamines and the targets that responded to COVID-19 infection were identified by the Similarity Ensemble Approach (SEA), SwissTargetPrediction (STP), and PubChem, respectively. We described bubble charts, the Pathways-Targets-Antihistamines (PTA) network, and the protein–protein interaction (PPI) network on the RPackage via STRING database. Furthermore, we utilized the AutoDock Tools software to perform molecular docking tests (MDT) on the key targets and drugs to evaluate the network pharmacological perspective. The final 15 targets were identified as core targets, indicating that Neuroactive ligand–receptor interaction might be the hub-signaling pathway of antihistamines on COVID-19 via bubble chart. The PTA network was constructed by the RPackage, which identified 7 pathways, 11 targets, and 30 drugs. In addition, GRIN2B, a key target, was identified via topological analysis of the PPI network. Finally, we observed that the GRIN2B-Loratidine complex was the most stable docking score with −7.3 kcal/mol through molecular docking test. Our results showed that Loratadine might exert as an antagonist on GRIN2B via the neuroactive ligand–receptor interaction pathway. To sum up, we elucidated the most potential antihistamine, a key target, and a key pharmacological pathway as alleviating components against COVID-19, supporting scientific evidence for further research.

AbstractSARS-CoV-2 is a novel coronavirus responsible for the COVID-19 pandemic, in which acute respiratory infections are associated with high socio-economic burden. We applied high-content screening to a well-defined collection of 5632 compounds including 3488 that have undergone previous clinical investigations across 600 indications. The compounds were screened by microscopy for their ability to inhibit SARS-CoV-2 cytopathicity in the human epithelial colorectal adenocarcinoma cell line, Caco-2. The primary screen identified 258 hits that inhibited cytopathicity by more than 75%, most of which were not previously known to be active against SARS-CoV-2 in vitro. These compounds were tested in an eight-point dose response screen using the same image-based cytopathicity readout. For the 67 most active molecules, cytotoxicity data were generated to confirm activity against SARS-CoV-2. We verified the ability of known inhibitors camostat, nafamostat, lopinavir, mefloquine, papaverine and cetylpyridinium to reduce the cytopathic effects of SARS-CoV-2, providing confidence in the validity of the assay. The high-content screening data are suitable for reanalysis across numerous drug classes and indications and may yield additional insights into SARS-CoV-2 mechanisms and potential therapeutic strategies.

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions.