In silico characterisation of bovine ephemeral fever virus alpha 1 protein, a potential viroporin; predictive modelling and molecular dynamic simulation

Bovine ephemeral fever (BEF) is a transient disease, but its high morbidity has economic consequences for milk production by cattle and buffaloes. Vaccines are available in several countries, including Israel, Australia, Turkey, and China; however, they have limited availability in India. Currently, no specific antivirals have been developed to treat BEFV. Instead, supportive treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) and calcium-magnesium supplements aid recovery. Viroporins are small hydrophobic transmembrane proteins known to perform crucial functions in viral pathogenesis, making them promising antiviral targets. A few previous studies identified the viroporin-like properties of bovine ephemeral fever virus (BEFV) encoded α1 protein. However, the structural features of α1 and the molecular mechanisms of pore formation are poorly understood. Here, we explored and characterised the 3D structure and predicted the potential oligomeric state of BEFV a1 using in silico approaches. Initially, protein physicochemical characterisation, modelling, in silico validation, and molecular dynamics simulation were performed to predict a reliable monomer model. Further, the ion channel/pore-forming pentamer structure of α1 was predicted, and the membrane-protein complex was generated. Interestingly, the predicted pentamer remained relatively stable throughout the molecular dynamics simulation and supported the hypothesis of α1 being a pore-forming single-pass transmembrane protein. These findings could aid in better understanding the role of α1 protein in BEFV pathogenesis and pave the way for developing novel or repurposing existing antiviral drugs against BEFV α1 in the future.