Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus

V. Karthick; N. Nagasundaram; C. George Priya Doss; Chiranjib Chakraborty; R. Siva; Aiping Lu; Ge Zhang; Hailong Zhu

doi:10.1186/s40249-016-0105-1

Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus

V. Karthick, N. Nagasundaram, C. George Priya Doss, Chiranjib Chakraborty, R. Siva, Aiping Lu, Ge Zhang, Hailong Zhu^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

46 Citations (Scopus)

Abstract

Background: The Ebola virus is highly pathogenic and destructive to humans and other primates. The Ebola virus encodes viral protein 40 (VP40), which is highly expressed and regulates the assembly and release of viral particles in the host cell. Because VP40 plays a prominent role in the life cycle of the Ebola virus, it is considered as a key target for antiviral treatment. However, there is currently no FDA-approved drug for treating Ebola virus infection, resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration.

Methods: This study aimed to screen the effective lead candidate against Ebola infection. First, the lead molecules were filtered based on the docking score. Second, Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates. Finally, molecular dynamics simulations was performed to validate the lead compound.

Results: Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40, and displays good pharmacokinetic properties.

Conclusion: This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection.

Original language	English
Article number	12
Number of pages	10
Journal	Infectious Diseases of Poverty
Volume	5
Issue number	1
DOIs	https://doi.org/10.1186/s40249-016-0105-1
Publication status	Published - 17 Feb 2016

Scopus Subject Areas

Public Health, Environmental and Occupational Health
Infectious Diseases

User-Defined Keywords

Ebola
Molecular docking
Molecular dynamics
Traditional Chinese Medicine Database
VP40

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s40249-016-0105-1

Cite this

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abstract = "Background: The Ebola virus is highly pathogenic and destructive to humans and other primates. The Ebola virus encodes viral protein 40 (VP40), which is highly expressed and regulates the assembly and release of viral particles in the host cell. Because VP40 plays a prominent role in the life cycle of the Ebola virus, it is considered as a key target for antiviral treatment. However, there is currently no FDA-approved drug for treating Ebola virus infection, resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration. Methods: This study aimed to screen the effective lead candidate against Ebola infection. First, the lead molecules were filtered based on the docking score. Second, Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates. Finally, molecular dynamics simulations was performed to validate the lead compound. Results: Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40, and displays good pharmacokinetic properties. Conclusion: This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection.",

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author = "V. Karthick and N. Nagasundaram and Doss, {C. George Priya} and Chiranjib Chakraborty and R. Siva and Aiping Lu and Ge Zhang and Hailong Zhu",

note = "Funding Information: This work was supported by the Research Grants Council of Hong Kong [212613] and Faculty Research Grant [FRG2/14-15/063]. The authors thank for the support of VIT and Galgotias University. Publisher copyright: {\textcopyright} 2016 Karthick et al. ",

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AU - Siva, R.

AU - Lu, Aiping

AU - Zhang, Ge

AU - Zhu, Hailong

N1 - Funding Information: This work was supported by the Research Grants Council of Hong Kong [212613] and Faculty Research Grant [FRG2/14-15/063]. The authors thank for the support of VIT and Galgotias University. Publisher copyright: © 2016 Karthick et al.

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N2 - Background: The Ebola virus is highly pathogenic and destructive to humans and other primates. The Ebola virus encodes viral protein 40 (VP40), which is highly expressed and regulates the assembly and release of viral particles in the host cell. Because VP40 plays a prominent role in the life cycle of the Ebola virus, it is considered as a key target for antiviral treatment. However, there is currently no FDA-approved drug for treating Ebola virus infection, resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration. Methods: This study aimed to screen the effective lead candidate against Ebola infection. First, the lead molecules were filtered based on the docking score. Second, Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates. Finally, molecular dynamics simulations was performed to validate the lead compound. Results: Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40, and displays good pharmacokinetic properties. Conclusion: This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection.

AB - Background: The Ebola virus is highly pathogenic and destructive to humans and other primates. The Ebola virus encodes viral protein 40 (VP40), which is highly expressed and regulates the assembly and release of viral particles in the host cell. Because VP40 plays a prominent role in the life cycle of the Ebola virus, it is considered as a key target for antiviral treatment. However, there is currently no FDA-approved drug for treating Ebola virus infection, resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration. Methods: This study aimed to screen the effective lead candidate against Ebola infection. First, the lead molecules were filtered based on the docking score. Second, Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates. Finally, molecular dynamics simulations was performed to validate the lead compound. Results: Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40, and displays good pharmacokinetic properties. Conclusion: This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection.

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Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus

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