In vitro characterization of the furin inhibitor MI-1851: Albumin binding, interaction with cytochrome P450 enzymes and cytotoxicity

Pászti-Gere, Erzsébet; Szentkirályi-Tóth, Anna; Szabó, Pál; Steinmetzer, Torsten; Fliszár-Nyúl, Eszter; Poór, Miklós

doi:10.1016/j.biopha.2022.113124

Cited by 7 publications

(2 citation statements)

References 26 publications

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“…Paszti-Gere et al revealed that another furin inhibitor, MI-1851, could exert anti-SARS-CoV-2 effects on cells by suppressing the cleavage of S protein. 194 …”

Section: Covid-19 Therapeutic Targets For Small Moleculesmentioning

confidence: 99%

Small molecules in the treatment of COVID-19

Lei

Chen

Jin

et al. 2022

Sig Transduct Target Ther

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The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.

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“…Paszti-Gere et al revealed that another furin inhibitor, MI-1851, could exert anti-SARS-CoV-2 effects on cells by suppressing the cleavage of S protein. 194 …”

Section: Covid-19 Therapeutic Targets For Small Moleculesmentioning

confidence: 99%

Small molecules in the treatment of COVID-19

Lei

Chen

Jin

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Moreover, SARS‐CoV‐2 infection was strongly inhibited by the Furin inhibitor, MI‐1851, in human airway epithelial cells. A combination TMPRSS2 inhibitors with inhibitors of Furin exhibited more potent activity against SARS‐CoV‐2 than any monotherapy, 56,66 suggesting therapeutic potential of Furin for treatment of COVID‐19. In addition, Furin is considered to be an important mediator of T cells, including regulatory T cell (Treg) and T helper type 1 cells, through restricting TGFβ‐1 and interferon‐γ (IFN‐γ) signaling 67,68 .…”

Section: Potential Pathogenic Targets Of Sars‐cov‐2 For Antiviral The...mentioning

confidence: 99%

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

Xue

Mei

Chen

et al. 2023

MedComm

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The coronavirus disease 2019 (COVID‐19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure. In the fight against viruses, the combination of viral genome sequencing, elucidation of the structure of viral proteins, and identifying proteins that are highly conserved across multiple coronaviruses has revealed many potential molecular targets. In addition, the time‐ and cost‐effective repurposing of preexisting antiviral drugs or approved/clinical drugs for these targets offers considerable clinical advantages for COVID‐19 patients. This review provides a comprehensive overview of various identified pathogenic targets and pathways as well as corresponding repurposed approved/clinical drugs and their potential against COVID‐19. These findings provide new insight into the discovery of novel therapeutic strategies that could be applied to the control of disease symptoms emanating from evolving SARS‐CoV‐2 variants.

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