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Title

Molecular docking enabled updated screening of the matrix protein VP40 from Ebola virus with millions of compounds in the MCULE database for potential inhibitors

 

Authors

Hasanain Abdulhameed Odhar*, Ali Mahmood Rayshan, Salam Waheed Ahjel, Alaa Abduljabbar
Hashim, Ali A. Mohammed Ali Albeer

 

Affiliation

Department of pharmacy, Al-Zahrawi University College, Karbala, Iraq

 

Email

Hasanain Abdulhameed Odhar – Phone: 9647725300923; Email: hodhar3@gmail.com; *Corresponding author

 

Article Type

Research Article

 

Date

Received September 12, 2019; Revised September 27, 2019; Accepted September 30, 2019; Published October 8, 2019

 

Abstract

Ebola virus is known for several outbreaks of hemorrhagic fever in West Africa. This RNA virus is linked to high fatality and easy transmission. Recently, an effective vaccine and a monoclonal antibody cocktail have been introduced to combat Ebola virus infection. The matrix protein VP40 of Ebola virus is a known drug target and it is essential for viral life cycle through participation in RNA transcription as well as for the budding of the mature virus. It is known that residues phenylalanine 125 and arginine 134 of VP40 are involved in the interaction with RNA. Therefore, it is of interest to screen VP40 with millions of compounds at the mcule.com database for potential inhibitors. The output hits were ranked according to their minimum binding energy to matrix protein VP40. We further calculated the pharmacokinetics and toxicology properties for the best five hits using several predictive ADME analysis web tools. We report a candidate lead (compound #5: ((10R)-10-(4-hydroxyphenyl)-11,12,14,16-tetra azatetracyclo[7.7.0.02,7.011,15] hexadeca-1(16), 2(7),3,5,8,12,14-heptaen-8-ol)) with high drug-likeness score, promising lead-likeness behaviour and high median lethal dose. The candidate lead compound #5 engages in hydrogen bonding and hydrophobic interactions with VP40 active site residues. Thus, the lead compound #5 is recommended for further in vitro and in vivo validations for further consideration.

 

Keywords

Ebola virus, VP40, virtual screening, docking, lead-likeness, mcule.com.

 

Citation

Odhar et al. Bioinformation 15(9): 627-632 (2019)

 

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 
License This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.