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Thymosin-α1 binds with ACE and downregulates the expression of ACE2 in human respiratory epithelia.
Zhang, Yu-Hang; Wang, Wen-Yu; Pang, Xiao-Cong; Wang, Zhi; Wang, Cheng-Zhuo; Zhou, Hang; Zheng, Bo; Cui, Yi-Min.
  • Zhang YH; Institute of Clinical Pharmacology, Peking University First Hospital, 100191 Beijing, China.
  • Wang WY; Department of Pharmacy, Peking University First Hospital, 100034 Beijing, China.
  • Pang XC; School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China.
  • Wang Z; Institute of Clinical Pharmacology, Peking University First Hospital, 100191 Beijing, China.
  • Wang CZ; Department of Pharmacy, Peking University First Hospital, 100034 Beijing, China.
  • Zhou H; Department of Cardiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing, China.
  • Zheng B; School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China.
  • Cui YM; School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China.
Front Biosci (Landmark Ed) ; 27(2): 48, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1772157
ABSTRACT

BACKGROUND:

Thymosin-α1 has been implicated into the treatment of novel respiratory virus Coronavirus Disease 2019 (COVID-19), but the underlying mechanisms are still disputable.

AIM:

Herein we aimed to reveal a previously unrecognized mechanism that thymosin-α1 prevents COVID-19 by binding with angiotensin-converting enzyme (ACE), which was inspired from the tool of network pharmacology.

METHODS:

KEGG pathway enrichment of thymosin-α1 treating COVID-19 was analyzed by Database of Functional Annotation Bioinformatics Microarray Analysis, then core targets were validated by ligand binding kinetics assay and fluorometric detection of ACE and ACE2 enzymatic activity. The production of angiotensin I, angiotensin II, angiotensin (1-7) and angiotensin (1-9) were detected by enzyme linked immunosorbent assay.

RESULTS:

We found that thymosin-α1 impaired the expressions of angiotensin-converting enzyme 2 and angiotensin (1-7) of human lung epithelial cells in a dose-dependent way (p < 0.001). In contrast, thymosin-α1 had no impact on their ACE and angiotensin (1-9) expressions but significantly inhibited the enzymatic activity of ACE (p > 0.05).

CONCLUSION:

The bioinformatic findings of network pharmacology and the corresponding pharmacological validations have revealed that thymosin-α1 treatment could decrease ACE2 expression in human lung epithelial cells, which strengthens the potential clinical applications of thymosin-α1 to prevent severe acute respiratory syndrome coronavirus 2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment Type of study: Prognostic study Limits: Humans Language: English Journal: Front Biosci (Landmark Ed) Year: 2022 Document Type: Article Affiliation country: J.fbl2702048

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment Type of study: Prognostic study Limits: Humans Language: English Journal: Front Biosci (Landmark Ed) Year: 2022 Document Type: Article Affiliation country: J.fbl2702048