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X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro),...

Structural insights into preinitiation complex assembly on core promoters

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase (Pol) II-mediated eukaryotic transcription. Here, we determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive...

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera...

Reckoning with Asian America

Diversity and functional landscapes in the microbiota of animals in the wild

Animals in the wild are able to subsist on pathogen-infected and poisonous food and show immunity to various diseases. These may be due to their microbiota, yet we have a poor understanding of animal microbial diversity and function. We used metagenomics to analyze the gut microbiota of over 180 species in the wild, covering diverse classes, feeding...

Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+ T cells recognizing epitopes presented by major histocompatibility complex (MHC)-II and MHC-E, not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded...

The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia

Slovakia conducted multiple rounds of population-wide rapid antigen testing for SARS-CoV-2 in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% CI: 57-58%) within one week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for...

Timing the SARS-CoV-2 index case in Hubei province

Understanding when SARS-CoV-2 emerged is critical to evaluating our current approach to monitoring novel zoonotic pathogens and understanding the failure of early containment and mitigation efforts for COVID-19. We employed a coalescent framework to combine retrospective molecular clock inference with forward epidemiological simulations to determine...

Gate-controlled BCS-BEC crossover in a two-dimensional superconductor

Bardeen-Cooper-Schrieffer (BCS) superfluidity and Bose-Einstein condensation (BEC) are the two extreme limits of the ground state of the paired fermion systems. We report crossover behavior from the BCS limit to the BEC limit realized by varying carrier density in a two-dimensional (2D) superconductor, electron-doped layered material ZrNCl. The phase...

Structural impact on SARS-CoV-2 spike protein by D614G substitution

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion...

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