Drug design for hemagglutinin: Screening and molecular dynamics from traditional Chinese medicine database

Chang, Tung Ti; Sun, Mao; Chen, Hsin Yi; Tsai, Fuu Jen; Chen, Calvin Yu-Chian

doi:10.1016/j.jtice.2010.11.001

Cited by 14 publications

(14 citation statements)

References 26 publications

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“…Traditional Chinese medicine (TCM) has been used extensively for finding effective drugs [88], and we have successfully designed novel medicinal compounds and identified potential drug leads through traditional Chinese Medicine Database@Taiwan (TCM@Taiwan) [89]. Preliminary studies conducted in this lab show potential for TCM compounds to serve as neuramindase and hemagglutinin inhibitors individually [90][91][92][93][94][95]. In view of the current needs for drugs effective against native and mutant H1N1/09 and our promising preliminary results, the present study integrates the concept of ''dual targeting'' with the aforementioned computational tools and TCM in the attempt to identify dual-targeting inhibitors of H1N1 that may be useful for drug development.…”

Section: Author Summarymentioning

confidence: 99%

“…The ability of the de novo derivatives to form interactions with both Asp151 and Glu228 may account for the higher DockScores. Binding of the top three de novo derivatives to H1 site is detailed elsewhere [92]. The ability to bind with important H1 residues Asp103 and Arg238 [100] indicates the dual targeting possibility of the candidates.…”

Section: Characteristics Of De Novo Product Binding Posesmentioning

confidence: 99%

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Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

2011

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The H1N1 influenza pandemic of 2009 has claimed over 18,000 lives. During this pandemic, development of drug resistance further complicated efforts to control and treat the widespread illness. This research utilizes traditional Chinese medicine Database@Taiwan (TCM Database@Taiwan) to screen for compounds that simultaneously target H1 and N1 to overcome current difficulties with virus mutations. The top three candidates were de novo derivatives of xylopine and rosmaricine. Bioactivity of the de novo derivatives against N1 were validated by multiple machine learning prediction models. Ability of the de novo compounds to maintain CoMFA/CoMSIA contour and form key interactions implied bioactivity within H1 as well. Addition of a pyridinium fragment was critical to form stable interactions in H1 and N1 as supported by molecular dynamics (MD) simulation. Results from MD, hydrophobic interactions, and torsion angles are consistent and support the findings of docking. Multiple anchors and lack of binding to residues prone to mutation suggest that the TCM de novo derivatives may be resistant to drug resistance and are advantageous over conventional H1N1 treatments such as oseltamivir. These results suggest that the TCM de novo derivatives may be suitable candidates of dual-targeting drugs for influenza.

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Section: Author Summarymentioning

confidence: 99%

Section: Characteristics Of De Novo Product Binding Posesmentioning

confidence: 99%

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

2011

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“…Consequently, poultry farmers have to use a large amount of egg yolk immunoglobulin as an alternative remedy (Thornton and Pattison, 1975;Zhang and Jin, 2009;Rodriguez Vaquero et al, 2010). In the past, traditional Chinese medicines and herb extracts have been widely used against IBDV and other avian viruses (Sun et al, 2006;Chang et al, 2011). Fructus mume, which originated in China, has been widely cultivated in Asia for approximately 3,000 years.…”

Section: Introductionmentioning

confidence: 99%

Protocatechuic acid, a new active substance against the challenge of avian infectious bursal disease virus

Pang

Chen

et al. 2012

Poultry Science

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The present study aims to investigate the potential antiviral activity of protocatechuic acid (PCA) and its mechanism against infectious bursal disease virus (IBDV) infection. In the curative test, dosages of PCA of 40, 20, and 10 mg/kg, the survival rate was 90, 90, and 60%, respectively, and the BW gain was 36.63, 31.85, and 51.8%, respectively. The survival rate for the Astragalus polysaccharide (ASP) group was significantly lower than those of the birds treated with 20 mg/kg or 40 mg/kg of PCA. The bursa indeces of chickens in 40 mg/kg, 20 mg/kg, and ASP groups were significantly higher than that of the infection group, whereas a significant increase of the spleen index was found in birds with 20 mg/kg PCA in comparison with other challenged groups. The birds treated with 20 mg/kg or 40 mg/kg of 3,4-dihydroxybenzoic acid also showed slightly higher levels of IBDV clearance in the bursa of Fabricius. Furthermore, the chickens treated with 20 mg/kg of PCA induced a significant lymphocyte proliferation and a significant increase in the CD4+/CD8+ ratio in comparison with the ASP chickens. These results imply that chickens treated with 20 mg/kg of PCA for 5 d could effectively induce active nonspecific immune responses against the IBDV infection.

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“…Virtual screening (VS) is a widely used method that has been shown to be successful in a variety of studies (Oprea & Matter 2004). In the past few years, many reports indicated that virtual screening techniques proved to be effective in making qualitative predictions that discriminated active from inactive compounds (Chen 2008; Chang et al 2011a; Chang et al 2011b; Lin et al 2011; Chang et al 2011c; Chang et al 2011d). The basic goal of the virtual screening is the reduction of the enormous virtual chemical space of small organic molecules, to synthesize and/or screen against a specific target protein, to a manageable number of the compound that inhibit a highest chance to lead to a drug candidate.…”

Section: Introductionmentioning

confidence: 99%

“…TCM pays more emphasis on systemic medication and subscribes medicines originated from natural herbs that give little or none side effects. Various research have been done on studying Chinese herbal medicine and studies suggest that it can aid in the cancer treatments especially head and neck cancer (Tou & 2012Chen ), solution for the stroke risk (Chang et al 2011f; Chen et al 2011; Chen & Chen 2011) and also for the flu treatment (Chang et al 2011c; Chang et al 2011d; Lin et al 2011a; Lai et al 2011; Chang et al 2011e; Lin et al 2011b; Chang et al 2011g). However, none of the earlier study reported the lead compound for the drug resistant target of influenza virus (H5N1).…”

Section: Introductionmentioning

confidence: 99%

Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach

Vasudevan

Ramanathan

2013

SpringerPlus

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The neuraminidase (NA) of the influenza virus is the target of antiviral drug, oseltamivir. Recently, cases are reported that Influenza virus becoming resistant to oseltamivir, necessitating the development of new long-acting antiviral compounds. Most importantly, H274Y mutation in neuraminidase exhibits high levels of resistance to oseltamivir. In this report, a novel class of lead molecule with potential NA inhibitory activity was found from the traditional Chinese medicine database (TCMD) using virtual screening approach. Initially ADME properties of the lead compounds were analyzed with respect to the Lipinski rule of five. Subsequently, the data reduction was carried out by employing molecular docking study. Final validation was done by means of molecular dynamic simulations. The toxicity profiles for the screened compound were also analyzed. The result indicates that neoglucobrassicin (a compound derived from TCMD) become a promising lead compound and be effective in treating oseltamivir-resistant influenza virus strains.

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Drug design for hemagglutinin: Screening and molecular dynamics from traditional Chinese medicine database

Cited by 14 publications

References 26 publications

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Two Birds with One Stone? Possible Dual-Targeting H1N1 Inhibitors from Traditional Chinese Medicine

Protocatechuic acid, a new active substance against the challenge of avian infectious bursal disease virus

Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach

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