Peroxide derivatives as SARS-CoV-2 entry inhibitors

Peroxide derivatives as SARS-CoV-2 entry inhibitors Full article

Journal

Virus Research
ISSN: 1872-7492 , E-ISSN: 0168-1702

Output data

Year: 2024, Volume: 340, Article number : 199295, Pages count : DOI: 10.1016/j.virusres.2023.199295

Authors

Zhang Ding-qi ¹ , Ma Qin-hai ² , Yang Meng-chu ¹ , Belyakova Yulia Yu. ³ , Yang Zi-feng ² , Radulov Peter S. ³ , Chen Rui-hong ¹ , Yang Li-jun ⁴ , Wei Jing-yuan ⁵ , Peng Yu-tong ⁵ , Zheng Wu-yan ¹ , Yaremenko Ivan A. ^6,3 , Terent'ev Alexander O. ³ , Coghi Paolo ⁵ , Wong Vincent Kam Wai ¹

Affiliations

1	Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
2	State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
3	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
4	Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China
5	School of Pharmacy, Macau University of Science and Technology, Macau, China
6	Faculty of Chemical and Pharmaceutical Technology and Biomedical Products, D .I . Mendeleev University of Chemical Technology of Russia, Moscow, Russian Federation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 – trioxolanes (ozonides), with the aim of identifying small molecules that interfere with the RBD-ACE2 interaction. We found that two compounds, compound 21 and 29, exhibit the activity to inhibit RBD-ACE2. They are further demonstrated to inhibit SARS-CoV-2 cell entry, as shown in pseudovirus assay and experiment with authentic SARS-CoV-2. A comprehensive in silico analysis was carried out to study the physicochemical and pharmacokinetic properties, revealing that both compounds have good physicochemical properties as well as good bioavailability. Our results highlight the potential of small molecules targeting RBD inhibitors as potential therapeutic drugs for COVID-19.

Zhang D-q. , Ma Q-h. , Yang M-c. , Belyakova Y.Y. , Yang Z-f. , Radulov P.S. , Chen R-h. , Yang L-j. , Wei J-y. , Peng Y-t. , Zheng W-y. , Yaremenko I.A. , Terent'ev A.O. , Coghi P. , Wong V.K.W.
Peroxide derivatives as SARS-CoV-2 entry inhibitors
Virus Research. 2024. V.340. 199295 . DOI: 10.1016/j.virusres.2023.199295 WOS Scopus OpenAlex

Web of science:	WOS:001137155800001
Scopus:	2-s2.0-85179612778
OpenAlex:	W4389635924

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