The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half(1) (https://www.who.org/). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clinical outcomes(2). Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approximately 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogues, the largest category of clinically used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogues synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clinical path forward.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population(1). Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies(2-10), the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.

Ferroelectricity in atomically thin bilayer structures has been recently predicted(1) and measured(2-4) in two-dimensional materials with hexagonal non-centrosymmetric unit-cells. The crystal symmetry translates lateral shifts between parallel two-dimensional layers to sign changes in their out-of-plane electric polarization, a mechanism termed 'slide-tronics'(4). These observations have been restricted to switching between only two polarization states under low charge carrier densities(5-12), limiting the practical application of the revealed phenomena(13). To overcome these issues, one should explore the nature of polarization in multi-layered van der Waals stacks, how it is governed by intra- and interlayer charge redistribution and to what extent it survives the addition of mobile charge carriers(14). To explore these questions, we conduct surface potential measurements of parallel WSe2 and MoS2 multi-layers with aligned and anti-aligned configurations of the polar interfaces. We find evenly spaced, nearly decoupled potential steps, indicating highly confined interfacial electric fields that provide a means to design multi-state 'ladder-ferroelectrics'. Furthermore, we find that the internal polarization remains notable on electrostatic doping of mobile charge carrier densities as high as 10(1)3 cm(-2), with substantial in-plane conductivity. Using density functional theory calculations, we trace the extra charge redistribution in real and momentum spaces and identify an eventual doping-induced depolarization mechanism.

There is a well-documented gap between the observed number of works produced by women and by men in science, with clear consequences for the retention and promotion of women(1). The gap might be a result of productivity differences(2-5), or it might be owing to women's contributions not being acknowledged(6,7). Here we find that at least part of this gap is the result of unacknowledged contributions: women in research teams are significantly less likely than men to be credited with authorship. The findings are consistent across three very different sources of data. Analysis of the first source-large-scale administrative data on research teams, team scientific output and attribution of credit-show that women are significantly less likely to be named on a given article or patent produced by their team relative to their male peers. The gender gap in attribution is present across most scientific fields and almost all career stages. The second source-an extensive survey of authors-similarly shows that women's scientific contributions are systematically less likely to be recognized. The third source-qualitative responses-suggests that the reason that women are less likely to be credited is because their work is often not known, is not appreciated or is ignored. At least some of the observed gender gap in scientific output may be owing not to differences in scientific contribution, but rather to differences in attribution.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities(1) that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities(2) map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades(2). Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.