Antiviral effects and tissue exposure of tetrandrine against SARS‐CoV‐2 infection and COVID‐19

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 (EC 90 ) in human lungs. This study provides insights into the route‐dependent pulmonary biodistribution of TET associated with its efficacy.

From Nature‐Sourced Polysaccharide Particles to Advanced Functional Materials

“…[239] Sacrificial templating utilizes a removable scaffold, which enables PSP adhesion to its surface or infiltration in scaffold's voids. [240] A variety of morphologies and surface topologies have been realized for materials containing ChNFs, [241] CNFs, [241] and CNCs. [242] For example, dissolution of polyvinyl alcohol (a sacrificial template) yielded a CNC-based porous material.…”

Tetrandrine Derivatives as Promising Antibacterial Agents

“…6,8−12 In addition, this alkaloid has been studied for the treatment of COVID-19, demonstrating in various clinical studies to be effective in improving the prognosis of patients and to have the potential to reduce the entry of SARS-CoV-2S pseudovirions. 13,14 Also, the antibacterial and antioxidant activity of tetrandrine has been reported, although these two properties have been poorly explored. 15−26 Regarding its antioxidant activity, tetrandrine is capable of trapping superoxide anion radicals at a concentration of 0.1 μg/mL, while at a concentration of 10 μg/mL, it causes a decrease in the consumption of hexosemonophosphate and hydrogen peroxide production.…”

“…Within this group, the isoquinoline alkaloids, those with an isoquinoline skeleton, have been very attractive to the scientific community and have therefore been extensively studied . The S , S -(+)-tetrandrine is a bisbenzylisoquinoline alkaloid that has diverse biological properties, being the antiproliferative activity in various cancer cell lines one of the most relevant, and has been extensively studied in the past decade. ,− In addition, this alkaloid has been studied for the treatment of COVID-19, demonstrating in various clinical studies to be effective in improving the prognosis of patients and to have the potential to reduce the entry of SARS-CoV-2S pseudovirions. , …”

“… 6 , 8 − 12 In addition, this alkaloid has been studied for the treatment of COVID-19, demonstrating in various clinical studies to be effective in improving the prognosis of patients and to have the potential to reduce the entry of SARS-CoV-2S pseudovirions. 13 , 14 …”