Prediction of specific virus outbreaks made from the increased concentration of a new class of virus genomic peptides, replikins.

Abstract

Advance warning of pathogen outbreaks has not been possible heretofore. A new class of genomic peptides associated with rapid replication was discovered and named replikins. Software was designed to analyze replikins quantitatively. Replikin concentration changes were measured annually prior to, and “real time” every few days during, the 2009 H1N1 influenza pandemic. Replikins were seen by both linear sequence representation and three-dimensional X-ray diffraction, and found to expand on the virus hemagglutinin surface prior to and during the H1N1 pandemic.A highly significant increased concentration of virus replikins was found a) retrospectively in three pandemics from 1918 to 1999 (14,227 sequences)(p<0.001), and b) prospectively before the H1N1 2009 pandemic (12,806 sequences) (in the hemagglutinin gene (N=8,046), p values by t-test = 1/10130, by linear regression = 1/1024 and 1/1029, by Spearman correlation < 2/1016, by Wilcoxon rank sum<1/1016, by multiple regression adjusting for correlation between consecutive years = 2/1022. Rising replikin concentration in H1N1 from 2006 to 2008, predicted one year in advance the H1N1 outbreak of 2009; and in H5N1, predicted the lethal outbreaks of H5N1 1997-2010.The possible combination of influenza strains H1N1 (high infectivity) and H5N1 (high lethality) is a matter of global concern (1,2). The risk of a combined H1N1 (high infectivity) - H5N1 (high lethality) outbreak may have increased because first, the Replikin Counts of the two virus strains have risen simultaneously, not seen previously; second, the rise is to the highest levels recorded since 1918 for H1N1, in Mexico (16.7), and since 1957 for H5N1, in Egypt (23.3); and third, clinical outbreaks of each strain are occurring in 2011. These simultaneous conditions may increase the risk that the two virus strains might come into contact with each other more frequently, facilitating transfer of genomic material to form a hybrid.

Bogoch Replikins Pandemic Prevention: Increase of Strain-Specific Influenza Genomic Replikin Counts, Having Predicted Outbreaks and their Location Seven Times Consecutively, Up to Two Years in Advance, Provides Time for Prevention of Pandemics

“…Earlier studies have shown that the increased concentration of a new class of virus genomic peptides, Replikins, precedes and predicts virus outbreaks (1). We now find that the area in the genome of the highest concentration of Replikins, and the country in which this peak exists in scout viruses, have permitted in the past five years seven consecutive accurate predictions of the geographic localization of coming outbreaks, including those now realized in Mexico for H1N1, and in Cambodia for H5N1.…”

“…When a high Count area in a sequence was found to be associated with high mortality rates, the high Count area was named Replikin Lethality Gene. The Replikin Count TM of these two genes in the H1N1 virus were determined annually from 2001 to 2008 before the pandemic, then during the pandemic 'real-time' every few days, then weekly, from April 2009 to February 2011 (1). Replikin peptides were visualized by two means: a) by linear display of sequences of contiguous numbered amino acids in the primary structure and b) by X-ray diffraction analysis of the 3-dimensional folded structure, which showed the increased coverage by Replikins of the HA gene surface in H1N1 real-time as the Replikin Count TM increased from 3.2 to 5.5 to 10.1 from before to during the course of the pandemic of 2009 (1).…”

“…In Figure 1, there is a greater proportion of the H5N1 virus population than that of H1N1 engaged in rapid replication. During low rate of replication 'rest periods' and small values of the mean Count (in blue), the SD (in red) is small or zero, as also observed with influenza B over many decades (1); during periods of rapid replication, the SD is larger in relation to the mean. Global Counts are those for all countries combined; Counts for Mexico and Cambodia are those in each country respectively.…”

“…(3,8,14). The current Replikins Count TM in Cambodia has not yet decreased, as it does when the outbreaks are over (1). Replikins Count TM warning may enable the prevention of emerging diseases rather than just waiting passively for the outbreak.…”

“…The size of the SD (in red) indicates the proportion of viruses in a given population with high Replikin Counts TM (previously associated with rapid replication (1,12)) and the diversity of the Replikin Counts TM (number of Replikins per 100 amino acids) in the genomes of a virus population (1). In Figure 1, there is a greater proportion of the H5N1 virus population than that of H1N1 engaged in rapid replication.…”