Elements of Higher Homotopy Groups Undetectable by Polyhedral Approximation

When nontrivial local structures are present in a topological space X, a common approach to characterizing the isomorphism type of the n-th homotopy group πn(X, x0) is to consider the image of πn(X, x0) in the nth Cˇ ech homotopy group πˇ n(X, x0) under the canonical homomorphism 9n : πn(X, x0) → πˇ n(X, x0). The subgroup ker(9n) is the obstruction to this tactic as it consists of precisely those elements of πn(X, x0), which cannot be detected by polyhedral approximations to X. In this paper, we use higher dimensional analogues of Spanier groups to characterize ker(9n). In particular, we prove that if X is paracompact, Hausdorff, and LCn−1, then ker(9n) is equal to the n-th Spanier group of X. We also use the perspective of higher Spanier groups to generalize a theorem of Kozlowski–Segal, which gives conditions ensuring that 9n is an isomorphism

Fragment screening targeting Ebola virus nucleoprotein C-terminal domain identifies lead candidates

The Ebola Virus is a causative agent of viral hemorrhagic fever outbreaks and a potential global health risk. The outbreak in West Africa (2013-2016) led to 11,000+ deaths and 30,000+ Ebola infected individuals. The current outbreak in the Democratic Republic of Congo (DRC) with 3000+ confirmed cases and 2000+ deaths attributed to Ebola virus infections provides a reminder that innovative countermeasures are still needed. Ebola virus encodes 7 open reading frames (ORFs). Of these, the nucleocapsid protein (eNP) encoded by the first ORF plays many significant roles, including a role in viral RNA synthesis. Here we describe efforts to target the C-terminal domain of eNP (eNP-CTD) that contains highly conserved residues 641-739 as a pan-Ebola antiviral target. Interactions of eNP-CTD with Ebola Viral Protein 30 (eVP30) and Viral Protein 40 (eVP40) have been shown to be crucial for viral RNA synthesis, virion formation, and virion transport. We used nuclear magnetic response (NMR)-based methods to screened the eNP-CTD against a fragment library. Perturbations of 1