Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation

Author:

Fuzo Carlos A.ORCID,Martins Ronaldo B.ORCID,Fraga-Silva Thais F.C.ORCID,Amstalden Martin K.ORCID,De Leo Thais CanassaORCID,Souza Juliano P.,Lima Thais M.ORCID,Faccioli Lucia H.ORCID,França Suzelei C.ORCID,Bonato Vania L.D.ORCID,Arruda EuricoORCID,Dias-Baruffi MarceloORCID

Abstract

AbstractThe global emergence of Covid-19 has caused huge human casualties. Clinical manifestations of the disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and non-homeostatic inflammatory response. In face of the urgent demand for effective drugs to treat Covid-19, we have searched for candidate compounds using a drug repurposing approach based on in silico analysis followed by biological validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F – a plant used in traditional Chinese medicine – as one of the best compounds out of 39 repurposed drug candidates. Celastrol reverted gene expression signature from SARS-CoV-2-infected cells; bound with high-affinity energy to viral molecular targets such as main protease (Mpro) and receptor-biding domain (RBD); inhibited SARS-CoV-2 replication in monkey (Vero and Vero-ACE2) and human (Caco-2 and Calu-3) cell lines; and decreased interleukin-6 (IL-6) secretion in SARS-CoV-2-infected human cell lines. Interestingly, celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity. Therefore, celastrol is a promising lead drug candidate to treat Covid-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells, two critical events in the pathophysiology of this disease.

Publisher

Cold Spring Harbor Laboratory

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Plant-Derived Compounds with Therapeutic Potential for the Treatment of Human Coronavirus Diseases;Proceedings of the National Academy of Sciences, India Section B: Biological Sciences;2024-06-20

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