ABSTRACT
Tetrandrine (TET) has been used to treat silicosis in China for decades. The aim of this study was to facilitate rational repurposing of TET against SARS-CoV-2 infection. In this study, we confirmed that TET exhibited antiviral potency against SARS-CoV-2 in the African green monkey kidney (Vero E6), human hepatocarcinoma (Huh7), and human lung adenocarcinoma epithelial (Calu-3) cell lines. TET functioned during the early-entry stage of SARS-CoV-2 and impeded intracellular trafficking of the virus from early endosomes to endolysosomes. An in vivo study that used adenovirus (AdV) 5-human angiotensin-converting enzyme 2 (hACE2)-transduced mice showed that although TET did not reduce pulmonary viral load, it significantly alleviated pathological damage in SARS-CoV-2-infected murine lungs. The systemic preclinical pharmacokinetics were investigated based on in vivo and in vitro models, and the route-dependent biodistribution of TET was explored. TET had a large volume of distribution, which contributed to its high tissue accumulation. Inhaled administration helped TET target the lung and reduced its exposure to other tissues, which mitigated its off-target toxicity. Based on the available human pharmacokinetic data, it appeared feasible to achieve an unbound TET 90% maximal effective concentration (EC90) in human lungs. This study provides insights into the route-dependent pulmonary biodistribution of TET associated with its efficacy.
ABSTRACT
In recent years, mass spectrometry (MS) is increasingly attracting interests for clinical applications, which also calls for technical innovations to make a transfer of MS from conventional analytical laboratories to clinics. The system design and analysis procedure should be friendly for novice users and appliable for on-site clinical diagnosis. In addition, the analysis result should be auto-interpreted and reported in formats much simpler than mass spectra. This motivates new ideas for developments in all the aspects of MS. In this review, we report recent advances of direct sampling ionization and miniature MS system, which have been developed targeting clinical and even point-of-care analysis. We also discuss the trend of the development and provide perspective on the technical challenges raised by diseases such as coronavirus SARS-CoV-2.
ABSTRACT
As the main active compound of Stephania tetrandra S. Moore, tetrandrine (TET) has been used to treat silicosis for nearly 50 years. TET has clear therapeutic effect on pulmonary fibrosis and lung cancer. A recent study suggests that TET may inhibit the replication of SARS-CoV-2 by blocking the two-pore channel 2 (TPC2), revealing its potential as a natural medicine to treat COVID-19. To explore the material basis of TET targeting lung efficacy and its potential toxicity, available literatures related to the pharmacological activity on pulmonary, dosage, toxicity and pharmacokinetics of TET are systemically reviewed. The prospect and current problems of TET to be a therapeutic agent for COVID-19 are further investigated on this basis.