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9The Nipah virus disease is a lethal infection that has led to 40% to 75% fatalities in Malaysia, 10 Bangladesh and India. The reports of human-to-human transmission documented in Bangladesh 11 has raised the specter of pandemic potential and has caused the World Health Organization to list 12 the Nipah virus as one of the pathogens to be considered for development of drugs and vaccines 13 on urgent basis, neither of which exist against the Nipah virus as of now, although many 14 proposals have been made and trials initiated. Given that there are established country-specific 15 differences in the virus' effects and fatalities, meeting the sudden need for a vaccine in case of an 16 epidemic will require design, development and preparation for a peptide vaccine. Thus, we 17 propose a protocol for creating peptide vaccines that can be tailor-made for these specific 18 countries, an approach which is being advocated for the first time. Here, we analyze the surface 19 proteins, Fusion protein and Glycoprotein, of the strains currently affecting the three countries on 20 a large scale and determine the specific country-based epitope differences. 21

We briefly review the situations arising out of epidemics that erupt rather suddenly, threatening life and livelihoods of humans. Ebola, Zika and the Nipah virus outbreaks are recent examples where the viral epidemics have led to considerably high degree of fatalities or debilitating consequences. The problems are accentuated by a lack of drugs or vaccines effective against the new and emergent viruses, and the inordinate amount of temporal and financial resources that are required to combat the novel pathogens. Progress in computational, biological and informational sciences have made it possible to consider design of synthetic vaccines that can be rapidly developed and deployed to help stem the damages. In this review, we consider the pros and cons of this new paradigm and suggest a new system where the manufacturing process can be decentralized to provide more targeted vaccines to meet the urgent needs of protection in case of a rampaging epidemic.

Human life has been at the edge of catastrophe for millennia due diseases which emerge and reemerge at random. The recent outbreak of the Zika virus (ZIKV) is one such menace that shook the global public health community abruptly. Modern technologies, including computational tools as well as experimental approaches, need to be harnessed fast and effectively in a coordinated manner in order to properly address such challenges. In this paper, based on our earlier research, we have proposed a four-pronged approach to tackle the emerging pathogens like ZIKV: (a) Epidemiological modelling of spread mechanisms of ZIKV; (b) assessment of the public health risk of newly emerging strains of the pathogens by comparing them with existing strains/pathogens using fast computational sequence comparison methods; (c) implementation of vaccine design methods in order to produce a set of probable peptide vaccine candidates for quick synthesis/production and testing in the laboratory; and (d) designing of novel therapeutic molecules and their laboratory testing as well as validation of new drugs or repurposing of drugs for use against ZIKV. For each of these stages, we provide an extensive review of the technical challenges and current state-of-the-art. Further, we outline the future areas of research and discuss how they can work together to proactively combat ZIKV or future emerging pathogens.

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Introduction: Among the mosquito-borne human-infecting flavivirus species that include Zika, West Nile, yellow fever, Japanese encephalitis and Dengue viruses, the Zika virus is found to be closest to Dengue virus, sharing the same clade in the Flavivirus phylogenetic tree. We consider these five flaviviruses and on closer examination in our analyses, the nucleotide sequences of the Dengue viral genes (envelope and NS5) and genomes are seen to be quite widely different from the other four flaviviruses. We consider the extent of this distinction and determine the advantage and/or disadvantage such differences may confer upon the Dengue viral pathogenesis. </P><P> Methods: We have primarily used a 2D graphical representation technique to show the differences in base distributions in these five flaviviruses and subsequently, obtained quantitative estimates of the differences. Similarity/dissimilarity between the viruses based on the genes were also determined which showed that the differences with the Dengue genes are more pronounced. Results: We found that the Dengue viruses compared to the other four flaviviruses spread rapidly worldwide and became endemic in various regions with small alterations in sequence composition relative to the host populations as revealed by codon usage biases and phylogenetic examination. We conclude that the Dengue genes are indeed more widely separated from the other aforementioned mosquito-borne human-infecting flaviviruses due to excess adenine component, a feature that is sparse in the literature. Such excesses have a bearing on drug and vaccine, especially peptide vaccine, development and should be considered appropriately.

IntroductionThe recent epidemic of the Zika virus in South and Central Americas have focused attention on the flavivirus group of viruses which also include all four types of Dengue virus (DENV1, DENV2, DENV3, DENV4), West Nile virus (WNV), Yellow fever virus (YFV) and Japanese encephalitis virus (JEV) besides Zika virus (ZIKV). All these viruses share strong homology at the protein sequence level, and slightly weaker homology at the nucleotide sequence level [1]. Phylogenetic studies place the four DENV serotypes in one clade and, ZIKV is found to be closest to DENV2. It is therefore widely held that ZIKV and DENV2 have the closest relationship among all the aforementioned flaviviruses [2].

The recent emergence of a highly lethal zoonotic virus, the Nipah virus, has raised concerns of a possible pandemic with high fatality ratios. While the similarities of the Malaysian and Bangladesh strains of the virus have been commented upon by various authors, the significant differences, if any, between the two strains that have led to starkly different fatality ratios of 40% and 75-100%, respectively, have not been satisfactorily addressed. In this report, we submit the results of our preliminary study of the strains as available from their complete genomes and show that the two strains are indeed different and should form part of a focused surveillance program.