However one might question whether effective compounds that

However, one might question whether effective compounds that do not bind to the C-terminal domain of PrP or that have other molecular targets besides PrP () will be excluded from this virtual screening. In the first case, docking with at least the 90–231 domain of the prion protein will prove useful. Besides, if PrP is the target for such compounds, there is an urgent need to address the three-dimensional structure of the most abundant (or repetitive structure) for the PrP Senexin B (). Molecular dynamics simulations indicated that parallel in-register intermolecular β-sheet architecture can be formed by PrP () and the use of a supercomputer (no longer for high-throughput screening) may allow identification of compounds that bind to PrP. That said, this is no easy challenge, and deserves attention from the scientific community, and especially biophysicists and computational biologists. Taking into account that the interaction of a compound with a specific region of the prion protein globular domain is a prerequisite for effective anti-scrapie activity (what is not always the case, as discussed above) the work published in provides a straightforward screening approach. In particular, it allows selection of compounds with IC values in the micromolar range from a library of more than 200,000 molecules. Although effective for different prion strains in infected-cells lines, the selected compounds did not increase survival of prion-infected mice (). This result reinforces the need for a thorough pharmacokinetic assessment of the most promising molecules. In general, this approach by may prove useful to screen for drugs against other diseases, mainly for those with a defined molecular target and a previously characterized binding region in the target protein.
Zika virus (ZIKV) is a flavivirus transmitted via the bites of infected mosquitoes, although non-vector-borne transmission has also been documented (sexual and maternofetal transmission and transmission through transfusion) (). Until the recent outbreaks, ZIKV had a known restricted circulation in Africa and Asia, but with only sporadic human cases reported. ZIKV infection was considered relatively benign, with the majority of infections causing no or mild symptoms. The most common clinical manifestations include rash, fever, arthralgia, and conjunctivitis. In 2007, Yap, Micronesia, was the first Zika outbreak outside Africa and Asia, but which was small and with no cases requiring hospitalization (). However, in 2013 a large Zika outbreak occurred in French Polynesia and then in New Caledonia in 2014 (), with first signs of the virus being associated with severe neurological complications, including Guillain-Barré syndrome () and microcephaly in newborns (), in a small percentage of cases. The virus then spread progressively to the Cook Islands, Easter Island and Solomon Islands prior to the explosive epidemic observed in Brazil and the Americas. In May 2015, the first local cases of Zika were recorded in Brazil and by December the number of cases had surpassed 1.5million. On February 2016, the World Health Organization declared Zika as a public health emergency of international concern and as of June 1st 60 countries reported on-going transmission.
Due to the growing population of people at advanced age, the number of patients affected by Alzheimer\'s disease (AD) is increasing tremendously. In 2015 about 46.8 million people suffered from AD worldwide which is estimated to increase to 131.5 million by 2050. Brains of AD patients all show a common histopathology; they are marked by an atrophy and degeneration that is caused by a severe loss of neurons and synapses (). Moreover, so-called extracellular senile plaques that consist of predominantly amyloid β (Aβ) peptides can be detected in the grey matter where they surround neurons. Since generation of Aβ peptides is hypothesized to play a major role in AD pathogenesis, it is essential to decipher the enzymatic cascade leading to the generation of Aβ. Most of the Aβ-peptides are initially generated by β-secretase (BACE1) with subsequent γ-secretase cleavage of the amyloid precursor protein (APP). In contrast, ADAM10 as α-secretase cleaves APP within the Aβ sequence and prevents the generation and subsequent accumulation of this neurotoxic peptide. Recently, several studies described the presence of N-terminally truncated Aβ peptides in brain or cerebrospinal fluid (CSF), including Aβ2–42, pyroglutamate Aβ3–42 (AβpE3–42) or Aβ4–42 (). However, BACE-1 is incapable in generating these truncated peptides, since it only cleaves APP in amino acid positions p1 or p11 of the Aβ peptide (). Therefore, it is of utmost importance to identify new players in APP metabolism that might have been overlooked so far, possibly due to low expression, lack of appropriate tools, or other experimental confounds.