A Computational Alternative to Analyze and Understand Ebola Virus Pathogenesis in Human

Students of Indian Institute of Technology Kharagpur, Abantika Pal, Anupam Banerjee won the award for research work of A Computational Alternative to Analyze and Understand Ebola Virus Pathogenesis in Human. They carried their project work under guidance of Dr. Pralay Mitra.

Zaire ebolavirus (EBOV), one of the most pathogenic species of Ebolavirus, is a significant threat to the human community according to the World Health Organization Ebola Situation Report. Several efforts have been made to design vaccines and therapeutic drugs without much success owing to the limited binding site residue information of human protein interacting with the viral protein (VP) molecules. Such limitations stem largely from the highly infectious nature of the virus that requires specialized personnel and bio-safety Level 4 laboratories to perform wet lab experiments. Although critical interactions involving the VPs and the human proteins responsible for innate/adaptive immune responses are discovered, specific binding information between such pairs is still unknown in most cases. Therefore, we proposed a protein interaction and protein design based computational alternative to identify critical residues crucial for the human protein-VP interactions. The computational framework used an existing protein design algorithm ensuring evolutionarily and energetically favorable mutations on interface residues of a participating protein in a protein complex. The VP24-KPNA5 (karyopherin alpha proteins 5) interaction is an experimentally well-studied phenomenon concerning EBOV pathogenesis and was therefore chosen to establish the efficacy of the proposed method. The critical residues identified in the VP24-KPNA5 interface by the proposed method were in excellent agreement with the previously reported experimental findings. Additionally, the mutations of the critical residues affected the overall stability of the complex because of a sharp decrease in both the number of hydrogen bonds and possible charge-charge interactions. Therefore, we propose that the computational framework could be extended to destabilize similar host-pathogen (like Human proteins interacting with Ebola:VP35) interactions, the critical interacting residues of which are to date unexplored.

Dr. Harsh Vardhan, Minister of Science and Technology, awarded the Gandhian Young Technological Innovation (GYTI) Appreciation to Abantika Pal, Anupam Banerjee, Indian Institute of Technology Kharagpur at the GYTI 2018 Awards function held at Rashtrapati Bhawan on March 19, 2018.

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