Current topics in medicinal chemistry
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Even after one year of its first outbreak reported in China, the coronavirus disease 2019 (COVID-19) pandemic is still sweeping the World, causing serious infections and claiming more fatalities. COVID-19 is caused by the novel coronavirus SARS-CoV-2, which belongs to the genus Betacoronavirus (β-CoVs), which is of greatest clinical importance since it contains many other viruses that cause respiratory disease in humans, including OC43, HKU1, SARS-CoV, and MERS. The spike (S) glycoprotein of β-CoVs is a key virulence factor in determining disease pathogenesis and host tropism, and it also mediates virus binding to the host's receptors to allow viral entry into host cells, i.e., the first step in virus lifecycle. ⋯ Herein, we mined the biomedical literature for viral entry inhibitors of other coronaviruses, with special emphasis on β-CoVs entry inhibitors. We also outlined the structural features of SARS-CoV-2 S protein and how it differs from other β-CoVs to better understand the structural determinants of S protein binding to its human receptor (ACE2). This review highlighted several promising viral entry inhibitors as potential treatments for COVID-19.
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Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular machines for viral host cell entry, genome replication and protein processing. Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak of SARS-CoV-2 in Wuhan, China in December 2019, novel and repurposed drugs were recently designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit the spread of SARS-CoV-2 and morbidity and mortality due to the COVID-19 pandemic.
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The advancement of cardiac surgery benefits from the continual technological progress of cardiopulmonary bypass (CPB). Every improvement in the CPB technology requires further clinical and laboratory tests to prove its safety and effectiveness before it can be widely used in clinical practice. In order to reduce the priming volume and eliminate a separate arterial filter in the CPB circuit, several manufacturers developed novel hollow-fiber membrane oxygenators with integrated arterial filters (IAF). ⋯ It can be easily set up and managed, simplifying the CPB circuit without sacrificing safety. An oxygenator with IAF is expected to be more beneficial to the patients with low body weight and when using a minimized extracorporeal circulation system. The aim of this review manuscript was to discuss briefly the concept of integration, the current oxygenators with IAF, and the in-vitro / in-vivo performance of the oxygenators with IAF.
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A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. ⋯ The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.