Inhibition of heat shock protein 90 suppresses <i>Bombyx mori</i> nucleopolyhedrovirus replication in <i>B. mori</i>

Shang, Qi; Wu, Ping; Huang, Haoling; Zhang, S.L.; Tang, Xudong; Guo, Xingchen

doi:10.1111/imb.12625

Cited by 22 publications

(20 citation statements)

References 41 publications

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“…It is not surprising to observe inhibition of SARS-CoV-2 by geldanamycin, given that a large number of viruses have been reported subject to geldanamycin inhibition. These include encephalomyocarditis virus (EMCV) (59), bombyx mori nucleopolyhedrovirus (60–62), pseudorabies virus (63), H5N1 influenza A virus (64), porcine circovirus 2 (65), chikungunya virus (66, 67), porcine reproductive and respiratory syndrome virus (68), enterovirus 71 (69, 70), herpes simplex virus type 2 (71), human cytomegalovirus (71, 72), Theiler’s murine encephalomyelitis virus (73), Ebola virus (74), hepatitis E virus (75), influenza virus (76), hepadnavirus (77), hepatitis B virus (77), flock house virus (78), vesicular stomatitis virus (79), hepatitis C virus (80, 81), herpes simplex virus type 1 (82, 83), vaccinia virus (84), RT and Rauscher leukemia virus (85). This broad antiviral activity of geldanamycin is primarily attributed to its antagonism of HSP90.…”

Section: Discussionmentioning

confidence: 99%

Anthracyclines inhibit SARS-CoV-2 infection

Wang

Pan²,

Ma³

et al. 2023

Preprint

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Vaccines and drugs are two effective medical interventions to mitigate SARS-CoV-2 infection. Three SARS-CoV-2 inhibitors, remdesivir, paxlovid, and molnupiravir, have been approved for treating COVID-19 patients, but more are needed, because each drug has its limitation of usage and SARS-CoV-2 constantly develops drug resistance mutations. In addition, SARS-CoV-2 drugs have the potential to be repurposed to inhibit new human coronaviruses, thus help to prepare for future coronavirus outbreaks. We have screened a library of microbial metabolites to discover new SARS-CoV-2 inhibitors. To facilitate this screening effort, we generated a recombinant SARS-CoV-2 Delta variant carrying the nano luciferase as a reporter for measuring viral infection. Six compounds were found to inhibit SARS-CoV-2 at the half maximal inhibitory concentration (IC50) below 1 mM, including the anthracycline drug aclarubicin that markedly reduced viral RNA-dependent RNA polymerase (RdRp)-mediated gene expression, whereas other anthracyclines inhibited SARS-CoV-2 by activating the expression of interferon and antiviral genes. As the most commonly prescribed anti-cancer drugs, anthracyclines hold the promise of becoming new SARS-CoV-2 inhibitors.

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Section: Discussionmentioning

confidence: 99%

Anthracyclines inhibit SARS-CoV-2 infection

Wang

Pan²,

Ma³

et al. 2023

Preprint

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“…However, the molecular mechanism of BmNPV‐host interaction is still poorly understood. Shang et al (2020) found that BmHSP90 inhibition by GA significantly reduced the BmNPV titer, the protein expression level of BmNPV nucleocapsid protein 39 (VP39), and the transcript level of BmNPV genes. Silencing the hsp90 gene in BmN cells suppressed BmNPV replication whereas overexpression of hsp90 promoted the replication of BmNPV, however, the mechanism is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence suggests that HSP90 is essential for the replication of various viruses. Our previous study indicated that inhibition of HSP90 by GA can suppress BmNPV proliferation in B. mori (Shang et al, 2020), but the mechanism is uncovered. In this study, we aim to explore the underlying molecular mechanism of HSP90 inhibitor in suppression of BmNPV proliferation from the aspect of miRNA.…”

Section: Introductionmentioning

confidence: 99%

Transcriptome of miRNA during inhibition of Bombyx mori nuclear polyhedrosis virus by geldanamycin in BmN cells

Zhao

Yin

Shen

et al. 2022

Arch Insect Biochem Physiol

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Bombyx mori nuclear polyhedrosis virus (BmNPV) is one of several viruses that cause great harm to the sericulture industry, and its pathogenic mechanism is still being explored. Geldanamycin (GA), a kind of HSP90 inhibitor, has been verified to suppress BmNPV proliferation. However, the molecular mechanism by which GA inhibits BmNPV is unclear. MicroRNAs (miRNAs) have been shown to play a key role in regulating virus proliferation and host‐pathogen interactions. In this study, BmN cells infected with BmNPV were treated by GA and DMSO for 72 h, respectively, then transcriptome analysis of miRNA was performed from the GA group and the control group. As a result, a total of 29 miRNAs were differentially expressed (DE), with 13 upregulated and 16 downregulated. Using bioinformatics analysis, it was found that the target genes of DEmiRNAs were involved in ubiquitin‐mediated proteolysis, phagosome, proteasome, endocytosis pathways, and so on. Six DEmiRNAs were verified by quantitative reverse‐transcription polymerase chain reaction. DElong noncoding RNA (DElncRNA)–DEmiRNA–messenger RNA (mRNA) regulatory networks involved in apoptosis and immune pathways were constructed in GA‐treated BmN cells, which included 12 DEmiRNA, 132 DElncRNA, and 69 mRNAs. This regulatory network enriched the functional role of miRNA in the BmNPV‐silkworm interactions and improved our understanding of the molecular mechanism of HSP90 inhibitors on BmNPV proliferation.

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“…Overexpression of BmSTAT in BmN cells increased the number of cells in the G2 phase of the cell cycle (54) and host resistance to BmNPV, but not to BmCPV (55). Additionally, inhibition of Hsp90 can cause upregulation of BmSTAT expression and suppression of BmNPV replication in the BmN cell (56), but it is not clear how Hsp90 can be linked to JAK/STAT. The extracellular ligand and effector molecules of this pathway in response to viral infection in silkworms have not been clearly identified and merit further investigation.…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

Insights Into the Antiviral Pathways of the Silkworm Bombyx mori

Jiang

2021

Front. Immunol.

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The lepidopteran model silkworm, Bombyx mori, is an important economic insect. Viruses cause serious economic losses in sericulture; thus, the economic importance of these viruses heightens the need to understand the antiviral pathways of silkworm to develop antiviral strategies. Insect innate immunity pathways play a critical role in the outcome of infection. The RNA interference (RNAi), NF-kB-mediated, immune deficiency (Imd), and stimulator of interferon gene (STING) pathways, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway are the major antiviral defense mechanisms, and these have been shown to play important roles in the antiviral immunity of silkworms. In contrast, viruses can modulate the prophenol oxidase (PPO), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the extracellular signal-regulated kinase (ERK) signaling pathways of the host to elevate their proliferation in silkworms. In this review, we present an overview of the current understanding of the main immune pathways in response to viruses and the signaling pathways modulated by viruses in silkworms. Elucidation of these pathways involved in the antiviral mechanism of silkworms furnishes a theoretical basis for the enhancement of virus resistance in economic insects, such as upregulating antiviral immune pathways through transgenic overexpression, RNAi of virus genes, and targeting these virus-modulated pathways by gene editing or inhibitors.

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Inhibition of heat shock protein 90 suppresses Bombyx mori nucleopolyhedrovirus replication in B. mori

Cited by 22 publications

References 41 publications

Anthracyclines inhibit SARS-CoV-2 infection

Anthracyclines inhibit SARS-CoV-2 infection

Transcriptome of miRNA during inhibition of Bombyx mori nuclear polyhedrosis virus by geldanamycin in BmN cells

Insights Into the Antiviral Pathways of the Silkworm Bombyx mori

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