Similarity is not enough: Tipping points of Ebola Zaire mortalities

• Ebola virus is the most deadly virus known.
• Bioinformatic scaling explains the subtype dependence of its virulence.
• The 2014 West Africa strain is only slightly mutated, but its very different properties can be explained by critical fluctuations.
• Structural considerations identify and explain an inverse correlation between virulence and transmissibility.

In early 2014 an outbreak of a slightly mutated Zaire Ebola subtype appeared in West Africa which is less virulent than 1976 and 1994 strains. The numbers of cases per year appear to be ∼1000 times larger than the earlier strains, suggesting a greatly enhanced transmissibility. Although the fraction of the 2014 spike glycoprotein mutations is very small (∼3%), the mortality is significantly reduced, while the transmission appears to have increased strongly. Bioinformatic scaling had previously shown similar inversely correlated trends in virulence and transmission in N1 (H1N1) and N2 (H3N2) influenza spike glycoprotein mutations. These trends appear to be related to various external factors (migration, availability of pure water, and vaccination programs). The molecular mechanisms for Ebola’s mutational response involve mainly changes in the disordered mucin-like domain (MLD) of its spike glycoprotein amino acids. The MLD has been observed to form the tip of an oligomeric amphiphilic wedge that selectively pries apart cell–cell interfaces via an oxidative mechanism.