Abstract Title:

Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2.

Abstract Source:

Int J Mol Sci. 2022 Oct 19 ;23(20). Epub 2022 Oct 19. PMID: 36293419

Abstract Author(s):

Mengjia Li, Yongzheng Zhang, Amir Zeb, Yang Wu, Lufeng Cheng

Article Affiliation:

Mengjia Li


Angiotensin-converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. However, inhibitors such as PAP-1 and bergamottin have been discovered; both of them can preferentially bind to ACE2, prevent RBD Spike S protein from binding to ACE2, and reduce the binding sites for RBD Spike S protein. In addition, we investigated the binding energy of PAP-1 and bergamottin with ACE2 through molecular docking with bio-layer interferometry (BLI) and found relatively high binding affinity (KD = 48.5 nM, 53.1 nM) between the PAP-1 and bergamottin groups. In addition, the nanomolar fraction had no effect on growth of the AT-II cell, but 150µM PAP-1 and 75µM bergamottin inhibited the proliferation of AT-II cells in vitro by 75% and 68%, respectively. Meanwhile, they significantly reduced ACE2 mRNA and proteins by 67%, 58% and 55%, 41%, respectively. These results indicate that psoralen compounds PAP-1 and bergamottin binding to ACE2 protein could be further developed in the fight against COVID-19 infection during the current pandemic. However, attention should be paid to the damage to human alveolar type II epithelial cells.

Study Type : In Vitro Study

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Sayer Ji
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