Discovery and Nanosized Preparations of (<i>S</i>,<i>R</i>)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.
Wang Z, Ye F, Feng Y, Xiao W, Song H, Zhao L, Lu R, Huang B, Liu Y, Wang W, Li Y, Ding Y, Zheng Y, Song X, Tan W, Wang Q.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(<i>S</i>,<i>R</i>), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC<sub>50</sub> 0.03 μM <i>in vitro</i>, which is substantially lower than that of remdesivir (EC<sub>50</sub>: 0.8 μM <i>in vitro</i>), the only authorized drug to date. The histopathological research revealed that NK007(<i>S</i>,<i>R</i>) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(<i>S</i>,<i>R</i>), which also showed good efficacy (EC<sub>50</sub>: NP-NK007, 0.007 μM <i>in vitro</i>; LP-NK007, 0.014 μM <i>in vitro</i>). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine <i>Cynanchum komarovii AL,</i> offer a new skeleton for the development of anticoronavirus drug candidate.