A Hypothesis Expanded: Role of Ascorbate and Glucose in the Pathophysiology of Ebola Haemorrhagic Fever Considering Intracellular Factors and Viral Proteins Apart from the Envelope Glycoprotein

Glucose and ascorbate transport and their opposite effects on the physiological processes, explain the pathophysiology of the Ebola virus. The virus impairs intracellularly the interferon (IFN) signalling. The present article will focus on the viral factors (VP24, VP35, VP40 proteins, nucleoprotein NP) that operate in the inner of the cell, subsequently to the viral entry. The haemorrhagic fever syndrome could be understood as a state of oxidative stress, driven by hyperglycaemia and the activation of NF-kB pathway and inflammatory cytokines. High glucose levels in plasma contributes to oxidative stress. It has also an inhibitory effect on Interferon (IFN) signalling. Conversely, ascorbate can counteract the IFN blocking exerted by the virus and interfere virus budding. A treatment strategy would focus on the administration of ascorbate and glutathione, glucose or insulin at convenience, in order to maintain constant and normal levels of glucose in plasma, to combat the oxidative and inflammatory stress.