Discovery and evolution of 12N-substituted aloperine derivatives as anti-SARS-CoV-2 agents through targeting late entry stage.

So far, there is still no specific drug against COVID-19. Taking compound 1 with anti-EBOV activity as the lead, fifty-four 12N-substituted aloperine derivatives were synthesized and evaluated for the anti-SARS-CoV-2 activities using pseudotyped virus model. Among them, 8a exhibited the most potential effects against both pseudotyped and authentic SARS-CoV-2, as well as SARS-CoV and MERS-CoV, indicating a broad-spectrum anti-coronavirus profile. The mechanism study disclosed that 8a might block a late stage of viral entry, mainly via inhibiting host cathepsin B activity rather than directly targeting cathepsin B protein. Also, 8a could significantly reduce the release of multiple inflammatory cytokines in a time- and dose-dependent manner, such as IL-6, IL-1ß, IL-8 and MCP-1, the major contributors to cytokine storm. Therefore, 8a is a promising agent with the advantages of broad-spectrum anti-coronavirus and anti-cytokine effects, thus worthy of further investigation.

An HPLC method for the determination and pharmacokinetic study of lehmannine in rat plasma.

A high-performance liquid chromatographic (HPLC) method for determining lehmannine (LMN) in rat plasma was developed for application in the pharmacokinetics study. The plasma was deproteinized with acetonitrile that contained an internal standard and was separated from the aqueous layer by adding sodium chloride. The HPLC assay was carried out using a VP-ODS column at 40 degrees C. The mobile phase was acetonitrile-0.02 mol/L ammonium acetate buffer-triethylamine (35:65:0.04, v/v/v). The flow rate was 1.0 mL/min. The detection wavelength was set at 220 nm. The method was used to determine the concentration-time profiles of LMN in the plasma following oral administration or bolus injection of LMN aqueous solution. The pharmacokinetic parameters of LMN were calculated for the first time by Drug and Statistics 1.0 program.