Frontiers in pharmacology
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Frontiers in pharmacology · Jan 2020
ReviewResearch Progress of Genetic Structure, Pathogenic Mechanism, Clinical Characteristics, and Potential Treatments of Coronavirus Disease 2019.
Coronavirus disease 2019 (COVID-19) is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and currently affects more than 8 million people worldwide. SARS-CoV-2 mainly invades the cells by binding to the angiotensin converting enzyme 2 (ACE2) receptor, leading to the injury of respiratory system, cardiovascular system, digestive system, and urinary system, and even secondary to acute respiratory distress syndrome (ARDS) and systemic inflammatory response, resulting in multiple organ failure. In this review, mainly focusing on biogenesis and pathogenic mechanisms, we describe the recent progress in our understanding of SARS-CoV-2 and then summarize and discuss its crucial clinical characteristics and potential mechanism in different systems. Additionally, we discuss the potential treatments for COVID-19, aiming at a better understanding of the pathogenesis of SARS-CoV-2 and providing new ideas for the personalized treatment of COVID-19.
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Frontiers in pharmacology · Jan 2020
ReviewMolecular Insights Into SARS COV-2 Interaction With Cardiovascular Disease: Role of RAAS and MAPK Signaling.
In December 2019, reports of viral pneumonia came out of Wuhan city in Hubei province in China. In early 2020, the causative agent was identified as a novel coronavirus (CoV) sharing some sequence similarity with SARS-CoV that caused the severe acute respiratory syndrome outbreak in 2002. The new virus, named SARS-CoV-2, is highly contagious and spread rapidly across the globe causing a pandemic of what became known as coronavirus infectious disease 2019 (COVID-19). ⋯ Here, we offer an overview of the proposed molecular pathways shared by the pathogenesis of CVD and SARS-CoV infections in order to provide a mechanistic framework for the observed interrelation. We examine the crosstalk between the renin-angiotensin-aldosterone system and mitogen activated kinase pathways that potentially links cardiovascular predisposition and/or outcome to SARS-CoV-2 infection. Finally, we summarize the possible effect of currently available drugs with known cardiovascular benefit on these pathways and speculate on their potential utility in mitigating cardiovascular risk and morbidity in COVID-19 patients.
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Frontiers in pharmacology · Jan 2020
ReviewPimavanserin: A Novel Antipsychotic With Potentials to Address an Unmet Need of Older Adults With Dementia-Related Psychosis.
Dementia affects more than 40 million people worldwide. When it is accompanied by psychosis, symptom management is especially challenging. Although no drug has been approved by the US Food and Drug Administration (FDA) for psychosis in patients with dementia, atypical antipsychotics are used off-label in severe cases in patients who do not respond to non-pharmacological interventions. ⋯ Topline result of the pivotal phase III HARMONY (NCT03325556) trial suggests that pimavanserin reduces the relapse of psychosis by 2.8-folds compared to placebo. This favorable result may open path for the potential approval of pimavanserin in DRP. In this review, we discuss the pharmacological activity, clinical efficacy and safety of pimavanserin as a novel atypical antipsychotic with potentials to address the unmet needs of older adults with DRP.
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Frontiers in pharmacology · Jan 2020
ReviewPD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake.
Cancer has been a major global health problem due to its high morbidity and mortality. While many chemotherapy agents have been studied and applied in clinical trials or in clinic, their application is limited due to its toxic side effects and poor tolerability. ⋯ Various novel promising approaches are now in clinical trials, just as icing on the cake. This review summarizes relevant investigations on combinatorial therapeutics based on PD-1/PD-L1 inhibition.
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Frontiers in pharmacology · Jan 2020
ReviewPathophysiology and Potential Therapeutic Candidates for COVID-19: A Poorly Understood Arena.
Coronavirus disease 2019 (COVID-19), an acute onset pneumonia caused by a novel Betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in the Wuhan City of China in December 2019 and evolved into a global pandemic. To date, there are no proven drugs or vaccines against this virus. Hence, the situation demands an urgent need to explore all potential therapeutic strategies that can be made available to prevent the disease progression and improve patient outcomes. ⋯ Moreover, there is a need to clearly define the patient populations who warrant therapy and also the timing of initiation of treatment. Understanding the disease pathology responsible for the clinical manifestations of COVID-19 is imperative to identify the potential targets for drug development. This review explains the pathophysiology of COVID-19 and summarizes the potential treatment candidates, which can provide guidance in developing effective therapeutic strategies.