Marburg VP24 Protein K-loop Cysteine Interactions with the Human Keap1 Protein

Marburg and Ebola viruses are pathogenic viruses that belong to the Filovirus family and have up to 90% fatality rates. The Marburg VP24 protein (mVP24), has been found to bind with the Human Keap1 protein, which allows the nuclear accumulation of Nrf2, activating the antioxidant response elements during the viral life cycle. In this work, we investigate the molecular level details of the interactions between Marburg and Ebola VP24 proteins and Keap1 using molecular dynamics simulation. Sequence alignment of Ebola and Marburg VP24 reveals that two cysteine residues are present in mVP24 protein but absent in the Ebola VP24 protein (eVP24). Our results show that the presence of cysteine residues in the K-loop region of Marburg VP24 protein makes binding with Keap1 stronger, forming hydrogen bonding and pi-interactions. These cysteine residues are absent in eVP24 protein, which does not bind with Keap1. These computational results provide insights into how Marburg but not Ebola, is able to bind with Keap1 protein and activate antioxidant response pathways.