&lt;i&gt;In vitro&lt;/i&gt; evaluation of the antiviral activity of methylglyoxal against influenza B virus infection

Charyasriwong, Siriwan; Haruyama, Takahiro; Kobayashi, Nobuyuki

doi:10.5582/ddt.2016.01045

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…BBGD increased the endogenous concentration of cellular MG by 4-fold to ca. 20 µM – a level similar to that which inhibited viral cytopathic activity ( Charyasriwong et al., 2016 ).…”

Section: Resultsmentioning

confidence: 77%

“…More recently, inhibition of cytopathic effect of strains of influenza B by MG was investigated. The most sensitive strain gave a median inhibitory concentration of 23 ± 7 µM MG ( Charyasriwong et al., 2016 ). These studies assessed antiviral activity by cytopathic response – concentration of MG required to prevent 50% lysis of infected cells, using relatively high multiplicity of infection (MOI).…”

Section: Resultsmentioning

confidence: 99%

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Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity—Opportunity for Repurposed Chemotherapy of COVID-19 Infection

et al. 2020

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The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments while effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 coronavirus predicted to be in functional domains, we examined which are activated toward modification by MG – residues with predicted or expected low pK a by neighboring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-CoV and MERS. Finally, w e identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.

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“…BBGD increased the endogenous concentration of cellular MG by 4-fold to ca. 20 µM – a level similar to that which inhibited viral cytopathic activity ( Charyasriwong et al., 2016 ).…”

Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity—Opportunity for Repurposed Chemotherapy of COVID-19 Infection

et al. 2020

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“…Although zanamivir demonstrated good antiviral activity, the susceptibility of A/Virginia/ATCC2/2009 and B/Lee/40 influenza viruses to this drug was lower than that of other viruses. These results could be explained by other studies that reported reduced efficacy of neuraminidase inhibitors against IBV [57,58], and resistance of A(H1N1)pdm09 influenza to oseltamivir [59,60]. Additionally, it has been suggested that oseltamivir exerts pharmacologic effects on the nervous system [61].…”

Section: Discussionmentioning

confidence: 86%

Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches

et al. 2017

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Influenza viruses have acquired resistance to approved neuraminidase-targeting drugs, increasing the need for new drug targets for the development of novel anti-influenza drugs. Nucleoprotein (NP) is an attractive target since it has an indispensable role in virus replication and its amino acid sequence is well conserved. In this study, we aimed to identify new inhibitors of the NP using a structure-based drug discovery algorithm, named Nagasaki University Docking Engine (NUDE), which has been established especially for the Destination for GPU Intensive Machine (DEGIMA) supercomputer. The hit compounds that showed high binding scores during in silico screening were subsequently evaluated for anti-influenza virus effects using a cell-based assay. A 4-hydroxyquinolinone compound, designated as NUD-1, was found to inhibit the replication of influenza virus in cultured cells. Analysis of binding between NUD-1 and NP using surface plasmon resonance assay and fragment molecular orbital calculations confirmed that NUD-1 binds to NP and could interfere with NP-NP interactions essential for virus replication. Time-of-addition experiments showed that the compound inhibited the mid-stage of infection, corresponding to assembly of the NP and other viral proteins. Moreover, NUD-1 was also effective against various types of influenza A viruses including a clinical isolate of A(H1N1)pdm09 influenza with a 50% inhibitory concentration range of 1.8–2.1 μM. Our data demonstrate that the combined use of NUDE system followed by the cell-based assay is useful to obtain lead compounds for the development of novel anti-influenza drugs.

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“…39,40 Moreover, MG and methylglyoxal-bis-guanylhydrazone have shown inhibitory effects against HIV and influenza virus. 41,42 None of the earlier studies have shown the effect of MG against fungal pathogens. In the present study, we determined the activity of MG and MGCN against C. albicans infection.…”

Section: Discussionmentioning

confidence: 99%

<p>Potential of Methylglyoxal-Conjugated Chitosan Nanoparticles in Treatment of Fluconazole-Resistant <em>Candida albicans</em> Infection in a Murine Model</p>

Khan

Younus

Allemailem

et al. 2020

IJN

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Background: Fungal infections are becoming more prevalent and threatening because of the continuous emergence of azole-resistant fungal infections. The present study was aimed to assess the activity of free Methylglyoxal (MG) or MG-conjugated chitosan nanoparticles (MGCN) against fluconazole-resistant Candida albicans. Materials and Methods: A novel formulation of MGCN was prepared and characterized to determine their size, shape and polydispersity index. Moreover, the efficacy of fluconazole or MG or MGCN was determined against intracellular C. albicans in macrophages and the systematic candidiasis in a murine model. The safety of MG or MGCN was tested in mice by analyzing the levels of hepatic and renal toxicity parameters. Results: Candida albicans did not respond to fluconazole, even at the highest dose of 20 mg/kg, whereas MG and MGCN effectively eliminated C. albicans from the macrophages and infected mice. Mice in the group treated with MGCN at a dose of 10 mg/kg exhibited a 90% survival rate and showed the lowest fungal load in the kidney, whereas the mice treated with free MG at the same dose exhibited 50% survival rate. Moreover, the administration of MG or MGCN did not induce any liver and kidney toxicity in the treated mice. Conclusion: The findings of the present work suggest that MGCN may be proved a promising therapeutic formulation to treat azole-resistant C. albicans infections.

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<i>In vitro</i> evaluation of the antiviral activity of methylglyoxal against influenza B virus infection

Cited by 21 publications

References 47 publications

Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity—Opportunity for Repurposed Chemotherapy of COVID-19 Infection

Vulnerabilities of the SARS-CoV-2 Virus to Proteotoxicity—Opportunity for Repurposed Chemotherapy of COVID-19 Infection

Identification of small molecule inhibitors for influenza a virus using in silico and in vitro approaches

<p>Potential of Methylglyoxal-Conjugated Chitosan Nanoparticles in Treatment of Fluconazole-Resistant <em>Candida albicans</em> Infection in a Murine Model</p>

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