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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Review
Progress in Studies on Structural and Remedial Aspects of Newly Born Coronavirus, SARS-CoV-2.
The article highlights an up-to-date progress in studies on structural and the remedial aspects of novel coronavirus 2019-nCoV, renamed as SARS-CoV-2, leading to the disease COVID-19, a pandemic. In general, all CoVs including SARS-CoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a Receptor-binding Domain (RBD) that mediates the binding to host cell receptor, Angiotensin Converting Enzyme 2 (ACE2). The article details the repurposing of some drugs to be tried for COVID-19 and presents the status of vaccine development so far. Besides drugs and vaccines, the role of Convalescent Plasma (CP) therapy to treat COVID-19 is also discussed.
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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.
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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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Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. ⋯ Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.