Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases

Silva, Taynara Lopes; Toffano, Leonardo; Fernandes, João B.; Silva, Maria Fátima das Graças Fernandes da; Sousa, Lorena Ramos Freitas de; Vieira, Paulo C.

doi:10.1007/s42770-020-00256-7

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…These differences could be attributed to the different affinity of TLR4 to BEA and LPS or by additional molecular targets of BEA within the cells. For example, Cathepsin B has recently been reported as a direct target of BEA (37). It is also known that Cathepsin B deficiency results in enhanced IL-12p40 production in dendritic cells by promoting the dendritic cell maturation (38).…”

Section: Discussionmentioning

confidence: 99%

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

et al. 2022

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Beauvericin (BEA), a mycotoxin of the enniatin family produced by various toxigenic fungi, has been attributed multiple biological activities such as anti-cancer, anti-inflammatory, and anti-microbial functions. However, effects of BEA on dendritic cells remain unknown so far. Here, we identified effects of BEA on murine granulocyte–macrophage colony-stimulating factor (GM-CSF)-cultured bone marrow derived dendritic cells (BMDCs) and the underlying molecular mechanisms. BEA potently activates BMDCs as signified by elevated IL-12 and CD86 expression. Multiplex immunoassays performed on myeloid differentiation primary response 88 (MyD88) and toll/interleukin-1 receptor (TIR) domain containing adaptor inducing interferon beta (TRIF) single or double deficient BMDCs indicate that BEA induces inflammatory cytokine and chemokine production in a MyD88/TRIF dependent manner. Furthermore, we found that BEA was not able to induce IL-12 or IFNβ production in Toll-like receptor 4 (Tlr4)-deficient BMDCs, whereas induction of these cytokines was not compromised in Tlr3/7/9 deficient BMDCs. This suggests that TLR4 might be the functional target of BEA on BMDCs. Consistently, in luciferase reporter assays BEA stimulation significantly promotes NF-κB activation in mTLR4/CD14/MD2 overexpressing but not control HEK-293 cells. RNA-sequencing analyses further confirmed that BEA induces transcriptional changes associated with the TLR4 signaling pathway. Together, these results identify TLR4 as a cellular BEA sensor and define BEA as a potent activator of BMDCs, implying that this compound can be exploited as a promising candidate structure for vaccine adjuvants or cancer immunotherapies.

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Section: Discussionmentioning

confidence: 99%

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

et al. 2022

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“…However, they are also associated with the production of beneficial compounds that inhibit the growth of phytopathogens affecting agricultural crops (Husaini et al, 2018). Some of the agricultural plants of significance that can be affected by Fusarium include pineapple (Silva et al, 2020), maize (Torovic, 2018), soybean (Schollenberger et al, 2007), and wheat (Orlando et al, 2019). As for Penicillium and Aspergillus, certain species within these genera are known to produce toxins and hold economic importance in the cereal industry (Alshannaq and Yu, 2017).…”

Section: Resultsmentioning

confidence: 99%

Thielaviopsis paradoxa and cultivable mycobiota associated with carapace of Rhynchophorus palmarum L. (Coleoptera: Curculionidae) in the state of Alagoas, Brazil

Calumby,

Almeida,

Eliziario

et al. 2023

Braz. J. Biol.

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Rhynchophorus palmarum (Coleoptera: Curculionidae) is a significant agricultural pest in palm plantations across tropical America, playing a critical role as a vector of the fungus Thielaviopsis paradoxa, which is the causative agent of stem bleeding disease in coconut palms. This disease has raised concerns due to its rapid spread and subsequent reduction in coconut production in northeastern Brazil. Additionally, this insect can establish mutualistic interactions with various fungi, including saprophytic, phytopathogenic, and entomopathogenic fungi, underscoring the importance of identifying its external mycobiota. The aim of this study was to assess the presence of T. paradoxa in the digestive tract and identify the cultivable mycobiota associated with the carapace of R. palmarum. To achieve this, a mycological study was conducted by culturing the external surface and digestive tract of field-caught adult insects (10 males and 10 females) on potato dextrose agar (PDA) in Maceió, Alagoas, Brazil. Fungal identification was performed by correlating microscopic features with the macroscopic characteristics of the obtained colonies. The results showed that T. paradoxa was detected in 15.0% of carapace isolates but was not found in the insects' intestinal tract. Additionally, nine fungal genera frequently associated with saprophytic or phytopathogenic behaviors were identified on the carapace. Eight of these genera belong to the Ascomycota phylum, while one is classified in the Basidiomycota phylum. The ubiquitous presence of Paecilomyces spp. and the occurrence of Trichosporon spp. in 95% of the assessed insects stand out. Furthermore, other potentially phytopathogenic fungi such as Penicillium spp., Fusarium spp., and Aspergillus spp., as well as fungi with entomopathogenic potential like Paecilomyces spp., Trichoderma spp., Metarhizium spp., and Beauveria bassiana, were detected. These findings enhance the understanding of the complex interactions between R. palmarum and its fungal hosts, providing insights for integrated pest management strategies.

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“…RMSF fluctuation of binding of Tinosponone with PLprowas shown in Fig. 3 (Silva et al 2020 ). The number of hydrogen bonds formed during 50 ns Molecular dynamic simulation was shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Genome sequencing revealed higher similarity with the previous SARS CoV (2003 outbreak). Both viruses share the same membrane-bound exopeptidase Angiotensin converting enzymes (ACE2) as the host receptor to enter the cells (Chakraborty and Member 2020 ; Silva et al 2020 ). Different structural proteins such as spike proteins play the main role in attachment to host receptors.…”

Section: Introductionmentioning

confidence: 99%

In-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2

Saranya¹,

Karunya²,

Varshini³

et al. 2022

Vegetos

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The SARS-Cov-2 virus, which is evolving continuously and causing adverse effects throughout the world, needs an effective drug molecule for its treatment. There are several receptors of SARS Cov-2 which are targeted for its inhibition by many lead molecules both in-vitro and in-vivo. Papain like Protease (PLpro) is one of the two SARS-Cov-2 proteases that can be used as a drug target for SARS Cov-2. It is a coronavirus enzyme that plays a role in the cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex and disruption of host responses. PLpro has also been linked to the cleavage of proteinaceous post translational modifications on host proteins as a means of evading antiviral immune responses. Structure-based drug discovery can be one of the effective methods to screen for various molecules against the target receptors. In this study, PLpro of SARS CoV-2 was chosen as the target for docking. Forty phytochemicals from various plant sources and four synthetic drugs have been screened for their inhibitory potential against PLpro using AutoDock Vina . Phytochemicals such as Tinosponone, Rhoifolin, Rosmanol, Berberin, Nimbin and two other existing drugs Elbasvir and Declatasvir showed higher inhibitory potential in terms of higher binding affinities. ADME and toxicity analysis were also performed to predict the pharmacokinetics and drug likeliness properties. It was concluded from the study that Tinosponone possesss potential inhibitor property of papain-like proteases (PLpro) of SARS CoV-2. Tinosponone from the plant Tinospora cordifolia had a binding affinity of − 9.3 kcal/mol and obeyed the Lipinski rules, making it an effective lead molecule for treating SARS CoV-2. Molecular Dynamics simulation of Tinosponone with PLpro has proved the stability and validity of the binding with RMSD value in range of 0.2 nm when it was run for 50 ns using GROMACS. Therefore, Tinosponone could be considered as a potential inhibitor of PLpro of SARS CoV-2.

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Mycotoxins from Fusarium proliferatum: new inhibitors of papain-like cysteine proteases

Cited by 9 publications

References 51 publications

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

Thielaviopsis paradoxa and cultivable mycobiota associated with carapace of Rhynchophorus palmarum L. (Coleoptera: Curculionidae) in the state of Alagoas, Brazil

In-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2

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