Twelve new Cephalotaxus alkaloids (1–12) and nine known analogues (13–21) were isolated and identified from the twigs and leaves of Cephalotaxus sinensis. The structures of new compounds (1–12) were elucidated...

Four undescribed biflavonoid alkaloids, sinenbiflavones A–D, were isolated from Cephalotaxus sinensis using a MS/MS‐based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR‐ESI‐MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A–D are the first examples of amentoflavone‐type (C‐3’–C‐8’’) biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C‐6‐methylated amentoflavone‐type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS‐CoV‐2 3CLpro inhibitory activity with 43 % inhibition rate at 40 μM.

One new compound and 13 known compounds were isolated from Aspergillus niger, a plant endophytic fungus of Pachysandra terminalis collected from Qinling Mountains, Xi'an, China. The structure of new compound 1 was classically determined by extensive spectroscopic analysis. Compounds 5, 6, 8, and 14 were firstly reported from Aspergillus, while compound 2 was isolated from A. niger for the first time. All isolated compounds were further evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 2 and 3 exhibited significant antioxidant activities with IC50 values of 31.64 μm and 24.32 μm, respectively, similar to the positive control ascorbic acid. Additionally, compound 1 displayed remarkable inhibitory activity against α-glucosidase with an IC50 value of 96.25 μm, which was 3.4-fold more potent than that of the positive control acarbose. Compound 1 has great potential for development as a new lead compound owing to its simple structure and remarkable biological activity.

Fusion with host cell membrane is the main mechanism of infection of SARS-CoV-2. Here, we propose a new strategy to double block SARS-CoV-2 membrane fusion by using Harringtonine (HT), a small-molecule antagonist. By using cell membrane chromatography (CMC), we found that HT specifically targeted the SARS-CoV-2 S protein and host cell TMPRSS2, and then confirmed that HT can inhibit pseudotyped virus membrane fusion. Furthermore, HT successfully blocked SARS-CoV-2 infection, especially in the delta and Omicron mutant. Since HT is a small-molecule antagonist, it is minimally affected by the continuous variation of SARS-CoV-2. Our findings show that HT is a potential small-molecule antagonist with a new mechanism of action against SARS-CoV-2 infection, and thus HT mainly targets the S protein, and thus, greatly reduces the damage of the S protein's autotoxicity to the organ system, has promising advantages in the clinical treatment of COVID-19.