Browsing by Subject "Shell disorder"

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    Rigidity of the Outer Shell Predicted by a Protein Intrinsic Disorder Model Sheds Light on the COVID-19 (Wuhan-2019-nCoV) Infectivity
    (MDPI, 2020-02-19) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladmir N.; Biochemistry and Molecular Biology, School of Medicine
    The world is currently witnessing an outbreak of a new coronavirus spreading quickly across China and affecting at least 24 other countries. With almost 65,000 infected, a worldwide death toll of at least 1370 (as of 14 February 2020), and with the potential to affect up to two-thirds of the world population, COVID-19 is considered by the World Health Organization (WHO) to be a global health emergency. The speed of spread and infectivity of COVID-19 (also known as Wuhan-2019-nCoV) are dramatically exceeding those of the Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV). In fact, since September 2012, the WHO has been notified of 2494 laboratory-confirmed cases of infection with MERS-CoV, whereas the 2002–2003 epidemic of SARS affected 26 countries and resulted in more than 8000 cases. Therefore, although SARS, MERS, and COVID-19 are all the result of coronaviral infections, the causes of the coronaviruses differ dramatically in their transmissibility. It is likely that these differences in infectivity of coronaviruses can be attributed to the differences in the rigidity of their shells which can be evaluated using computational tools for predicting intrinsic disorder predisposition of the corresponding viral proteins.
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    Zika and Flavivirus Shell Disorder: Virulence and Fetal Morbidity
    (MDPI, 2019-11-06) Goh, Gerard Kian-Meng; Dunker, A. Keith; Foster, James A.; Uversky, Vladimir N.; Biochemistry and Molecular Biology, School of Medicine
    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.