ABSTRACT
The coronavirus disease (COVID-19) pandemic, caused by SARS-CoV-2 coronavirus, is devastatingly impacting human health. A prominent component of COVID-19 is the infection and destruction of the ciliated respiratory cells, which perpetuates dissemination and disrupts protective mucociliary transport (MCT) function, an innate defense of the respiratory tract. Thus, drugs that augment MCT could improve the barrier function of the airway epithelium and reduce viral replication and, ultimately, COVID-19 outcomes. We tested five agents known to increase MCT through distinct mechanisms for activity against SARS-CoV-2 infection using a model of human respiratory epithelial cells terminally differentiated in an air/liquid interphase. Three of the five mucoactive compounds tested showed significant inhibitory activity against SARS-CoV-2 replication. An archetype mucoactive agent, ARINA-1, blocked viral replication and therefore epithelial cell injury; thus, it was further studied using biochemical, genetic, and biophysical methods to ascertain the mechanism of action via the improvement of MCT. ARINA-1 antiviral activity was dependent on enhancing the MCT cellular response, since terminal differentiation, intact ciliary expression, and motion were required for ARINA-1-mediated anti-SARS-CoV2 protection. Ultimately, we showed that the improvement of cilia movement was caused by ARINA-1-mediated regulation of the redox state of the intracellular environment, which benefited MCT. Our study indicates that intact MCT reduces SARS-CoV-2 infection, and its pharmacologic activation may be effective as an anti-COVID-19 treatment.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mucociliary Clearance , Respiratory System , Epithelial Cells , Virus ReplicationABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is an epidemic infectious disease resulted from 2019 novel coronavirus (2019-nCoV). Up till now, COVID-19 has swept globally. Currently, due to many high-profiled benefits, clinical studies on Toujie Quwen granule (TJQW) have been increasing. The aim of the study is to assess the efficacy and safety of TJQW used with conventional western therapy for COVID-19. METHODS: Relevant randomized controlled trials (RCTs) were searched in Chinese and English databases, and the search time is January 2020 to May 2021. English databases include PubMed, Embase, Web of Science, and the Cochrane Library. Chinese databases include CNKI, WF, VIP, and CBM. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched by us from January 2020 to May 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by 2 researchers independently. Statistical analysis will be conducted using the RevMan 5.3.5 software. After screening the literature based on the inclusion and exclusion criteria, The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality of each result. RESULTS: This study will provide the evidence for TJQW to be used with conventional western therapy for COVID-19. CONCLUSION: The efficacy and safety of TJQW used with conventional western therapy for COVID-19 will be assessed. INPLASY REGISTRATION NUMBER: INPLASY202150038.