Abediterol

The COVID-19 pandemic infection has claimed many lives and added to the social, economic, and psychological distress. The contagious disease has quickly spread to almost 218 countries and territories following the regional outbreak in China. As the number of infected populations increases exponentially, there is a pressing demand for anti-COVID drugs and vaccines. Virtual screening provides possible leads while extensively cutting down the time and resources required for ab-initio drug design. We report structure-based virtual screening of a hundred plus library of quinoline drugs with established antiviral, antimalarial, antibiotic or kinase inhibitor activity. In this study, targets having a role in viral entry, viral assembly, and viral replication have been selected. The targets include: 1) RBD of receptor-binding domain spike protein S 2) M^pro Chymotrypsin main protease 3) P^pro Papain protease 4) RNA binding domain of Nucleocapsid Protein, and 5) RNA Dependent RNA polymerase from SARS-COV-2. An in-depth analysis of the interactions and G-score compared to the controls like hydroxyquinoline and remdesivir has been presented. The salient results are (1) higher scoring of antivirals as potential drugs (2) potential of afatinib by scoring as better inhibitor, and (3) biological explanation of the potency of afatinib. Further MD simulations and MM-PBSA calculations showed that afatinib works best to interfere with the the activity of RNA dependent RNA polymerase of SARS-COV-2, thereby inhibiting replication process of single stranded RNA virus. Communicated by Ramaswamy H. Sarma.

Asthma, a heterogeneous disease, is characterized by chronic airway inflammation and hyperreactivity. β₂-adrenoreceptor agonists (β₂-agonists) remain pivotal for asthma management. Short-acting β₂-agonists (SABAs) result in rapid symptomatic alleviation and bronchospasm prevention. Patients experience significant clinical benefits from therapy with long-acting β₂-agonists (LABAs) with efficacy to bronchodilate, and prolonged lung function betterment. Recently discovered β₂-agonists with longer half-lives offer once-daily dosing.

The authors provide a thorough review of the pharmacokinetics, pharmacodynamics, efficacy, tolerability, classification, and safety of β₂-agonists through an in-depth review of current literature using these databases: U.S. National Institutes of Health's National Library of Medicine (NIH/NLM), PubMed Central, and NLM clinical trials.

β₂- agonists act primarily on airway smooth muscle cells and are quintessential for adequate asthma management. Given their pharmacodynamic and pharmacokinetic properties, SABAs are used as rescue medication. Notably, the current Global Initiative for Asthma (GINA) strategy document recommends using LABA/inhaled corticosteroid combinations both as a daily controller and as a rescue medication. Clinicians should assess this new treatment plan on a per-case basis, making sure to evaluate inhaler adherence and treat modifiable risk factors. The development of next-generation β₂- agonists is an exciting research area that could significantly improve patients' adherence to treatment regimens and, consequently, asthma control and quality of life.