A Comprehensive Response: The Role of Nonstate Actors in the Global Plan.

Nonstate actors-especially faith-based organizations, other nongovernmental organizations, groups of people living with HIV and AIDS, and private sector organizations-have been deeply committed to supporting governments reach the goals of the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan). This article highlights the role and contributions of select faith-based organizations and some private sector and philanthropic partners, as well as the work of other organizations. The success and impact of the Global Plan was in no small part a result of large-scale country-led collaboration in the provision of health care and implementation of programs. As the world grapples with meeting the ambitious United Nations Joint Programme on AIDS targets to end the AIDS epidemic by 2030-at a time when it also faces many other emerging health crises-the lessons learned from the Global Plan in harnessing the strengths of nonstate partners are the ones that should be replicated, enhanced, and taken to scale.

Structural basis for the function and inhibition of an influenza virus proton channel.

The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.