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Open AccessArticle

Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity

Goh’s BioComputing, Singapore 548957, Singapore
Center for Computational Biology, Indiana and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA
Institute for Bioinformatics and Evolutionary Studies, University of Idaho, Moscow, ID 83844, USA
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 710;
Received: 5 October 2019 / Revised: 29 October 2019 / Accepted: 4 November 2019 / Published: 6 November 2019
Zika virus (ZIKV) was first discovered in 1947 in Africa. Since then, sporadic ZIKV infections of humans have been reported in Africa and Asia. For a long time, this virus was mostly unnoticed due to its mild symptoms and low fatality rates. However, during the 2015–2016 epidemic in Central and South America, when millions of people were infected, it was discovered that ZIKV causes microcephaly in the babies of mothers infected during pregnancy. An examination of the M and C proteins of the ZIKV shell using the disorder predictor PONDR VLXT revealed that the M protein contains relatively high disorder levels comparable only to those of the yellow fever virus (YFV). On the other hand, the disorder levels in the C protein are relatively low, which can account for the low case fatality rate (CFR) of this virus in contrast to the more virulent YFV, which is characterized by high disorder in its C protein. A larger variation was found in the percentage of intrinsic disorder (PID) in the C protein of various ZIKV strains. Strains of African lineage are characterized by higher PIDs. Using both in vivo and in vitro experiments, laboratories have also previously shown that strains of African origin have a greater potential to inflict higher fetal morbidity than do strains of Asian lineage, with dengue-2 virus (DENV-2) having the least potential. Strong correlations were found between the potential to inflict fetal morbidity and shell disorder in ZIKV (r2 = 0.9) and DENV-2 (DENV-2 + ZIKV, r2 = 0.8). A strong correlation between CFR and PID was also observed when ZIKV was included in an analysis of sets of shell proteins from a variety of flaviviruses (r2 = 0.8). These observations have potential implications for antiviral vaccine development and for the design of cancer therapeutics in terms of developing therapeutic viruses that penetrate hard-to-reach organs. View Full-Text
Keywords: Zika; protein intrinsic disorder; shell disorder; dengue; virulence; microcephaly; vaccine; yellow fever; morbidity; fetal Zika; protein intrinsic disorder; shell disorder; dengue; virulence; microcephaly; vaccine; yellow fever; morbidity; fetal
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Goh, G. .-M.; Dunker, A.K.; Foster, J.A.; Uversky, V.N. Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity. Biomolecules 2019, 9, 710.

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