Effects of diarylbutane lignans from fruit on SARS-CoV-2 3CL and PL and their anti-inflammatory properties.

BACKGROUND

fruit is a well-known traditional Chinese medicine (TCM), whose extract has a potent inhibitory effect on the severe acute respiratory syndrome-coronavirus-2 (SARS‑CoV‑2) 3-chymotrypsin-like protease (3CL) and papain-like protease (PL).

PURPOSE

This work aims to find the active components from the fruit of against SARS‑CoV‑2 3CL and PL.

MATERIALS AND METHODS

The chemical constituents of the fruit of were retrieved based on the electronic databases, such as Web of Science, PubMed, Medline Plus, and CNKI. Molecular docking was used to screen the active components against SARS‑CoV‑2 3CL and PL. Potential hit compounds were further evaluated by enzymatic activity assay. Furthermore, the anti-inflammatory activities of the active compounds were further explored using the phorbol-12-myristate-13-acetate (PMA)-induced THP1 cells model.

RESULTS

In this work, we retrieved 75 components of fruit, including 62 dibenzocyclooctadiene-type lignans, 3 diarylbutane-type lignans, 2 tetrahydrofuran-type lignans, and 8 nortriterpenoids. Combining molecular docking study and experiments, we found that pregomisin (), meso‑dihydroguaiaretic acid (), and nordihydroguaiaretic acid () could potently inhibit 3CL with IC values of 3.07 ± 0.38, 4.12 ± 0.38, and 6.06 ± 0.62 μM, respectively, and inhibit PL with IC values of 5.23 ± 0.33, 4.24 ± 0.46, and 16.28 ± 0.54 μM, respectively. Interestingly, compounds , and also have potent activities of regulating the inflammatory response .

CONCLUSION

Our results suggest that compounds , and may be promising SARS-CoV-2 3CL and PL inhibitors and anti-inflammatory.