An outbreak of coronavirus disease 2019 (COVID-19) 1-3 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 4 , has spread globally. Countermeasures are needed to treat and prevent further dissemination of the virus. Here we report the isolation of two specific human monoclonal antibodies (termed CA1 and CB6) from a patient convalescing from COVID-19. CA1 and CB6 demonstrated potent SARS-CoV-2-specific neutralization activity in vitro. In addition, CB6 inhibited infection with SARS-CoV-2 in rhesus monkeys in both prophylactic and treatment settings. We also performed structural studies, which revealed that CB6 recognizes an epitope that overlaps with angiotensin-converting enzyme 2 (ACE2)-binding sites in the SARS-CoV-2 receptor-binding domain, and thereby interferes with virus-receptor interactions by both steric hindrance and direct competition for interface residues. Our results suggest that CB6 deserves further study as a candidate for translation to the clinic.

Named Data Networking (NDN) is one of five projects funded by the U.S. National Science Foundation under its Future Internet Architecture Program. NDN has its roots in an earlier project, Content-Centric Networking (CCN), which Van Jacobson first publicly presented in 2006. The NDN project investigates Jacobson's proposed evolution from today's host-centric network architecture (IP) to a data-centric network architecture (NDN). This conceptually simple shift has far-reaching implications for how we design, develop, deploy, and use networks and applications. We describe the motivation and vision of this new architecture, and its basic components and operations. We also provide a snapshot of its current design, development status, and research challenges. More information about the project, including prototype implementations, publications, and annual reports, is available on named-data.net.

Trifluorophenyl‐functionalized multi‐walled‐carbon‐nanotube/poly(vinylidene fluoride) (TFP‐MWNT/PVDF) nanocomposites are fabricated by employing a wet‐chemistry route. The modified MWNTs are observed to form a well‐dispersed, structurally random nanophase within the polymer matrix (see figure). The TFP‐MWNT/PVDF nanocomposite exhibits enhanced dielectric permittivity when the content of TFP‐MWNT is close to the percolation threshold.

The transthyretin amyloidoses (ATTR) are invariably fatal diseases characterized by progressive neuropathy and/or cardiomyopathy. ATTR are caused by aggregation of transthyretin (TTR), a natively tetrameric protein involved in the transport of thyroxine and the vitamin A–retinol-binding protein complex. Mutations within TTR that cause autosomal dominant forms of disease facilitate tetramer dissociation, monomer misfolding, and aggregation, although wild-type TTR can also form amyloid fibrils in elderly patients. Because tetramer dissociation is the rate-limiting step in TTR amyloidogenesis, targeted therapies have focused on small molecules that kinetically stabilize the tetramer, inhibiting TTR amyloid fibril formation. One such compound, tafamidis meglumine (Fx-1006A), has recently completed Phase II/III trials for the treatment of Transthyretin Type Familial Amyloid Polyneuropathy (TTR-FAP) and demonstrated a slowing of disease progression in patients heterozygous for the V30M TTR mutation. Herein we describe the molecular and structural basis of TTR tetramer stabilization by tafamidis. Tafamidis binds selectively and with negative cooperativity (K d s ∼2 nM and ∼200 nM) to the two normally unoccupied thyroxine-binding sites of the tetramer, and kinetically stabilizes TTR. Patient-derived amyloidogenic variants of TTR, including kinetically and thermodynamically less stable mutants, are also stabilized by tafamidis binding. The crystal structure of tafamidis-bound TTR suggests that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis.

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To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor ␣ (RAR␣) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G1/G0 arrest in APL cells through hitting multiple targets compared with the effects of mono-or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RAR␣ degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.traditional chinese medicine ͉ active ingredient ͉ tetraarsenic tetrasulfide ͉ synergism ͉ systems biology T he complexity of medicine suggests that treatment protocols should be carefully designed, and the construction of a prescription is an art in fighting disease. Increasing evidence demonstrates that, in treating illnesses, including cancer (1) and HIV/AIDS (2), treatment regimens containing multiple drugs with distinct but related mechanisms can usually amplify the therapeutic efficacies of each agent, leading to maximal therapeutic efficacy with minimal adverse effects. Interestingly, combination therapy has been advocated for Ͼ2,500 years by prescriptions called formulae (3, 4) in traditional Chinese medicine (TCM), a unique medical system assisting the ancient Chinese in dealing with disease. Typically, formulae consist of several types of medicinal herbs or minerals, in which one represents the principal component, and others serve as adjuvant ones to assist the effects or facilitate the delivery of the principal component (3, 4). It is believed that, at least in some formulae, multiple components could hit multiple targets and exert synergistic therapeutic efficacies (3, 4). However, essential compounds have not been identified in most formulae, whereas precise mechanisms of form...

In this letter, the dielectric properties of the untreated multiwall carbon-nanotubes∕poly(vinylidene fluoride) (MWNT∕PVDF) composites are studied. Towards low frequencies, the dielectric constant of a composite with about 2.0vol% of MWNT increases rapidly and the value of the dielectric constant is as high as 300. However, by a calculation, the percolation threshold of the MWNT∕PVDF composites is only 1.61vol% (0.0161 volume fraction) of MWNT. Both the large aspect ratio and the high conductivity of the MWNT may lead to the low percolation threshold of the MWNT∕PVDF composites. For the percolation composite, the dielectric loss value is always less than 0.4, irrespective of the frequency. Therefore, the experimental results suggest that the dielectric properties of MWNT∕PVDF composites may be improved significantly without the chemical functionalization to carbon nanotubes.