Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

Background: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)-biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

A reinvestigation of mono- and bis-ethynyl phosphonium salts: structural, computational studies and new reactivity

A series of mono- and bis-ethynyl phosphnium salts have been prepared via reaction of bromoacetylenes, Ph-C≡C-Br or Br-C≡C-C6H4-C≡C-Br, with various phosphines. Some of the derivatives reported are previously known, ([Ph-C≡C-PPh3]Br, [Ph-C≡C-PMe3]Br, [Ph-C≡C-PBu3]Br, and [Ph3P-C≡C-C6H4-C≡C-PPh3][Br2]), however typically these are missing complete spectroscopic characterization and many have been prepared using much more complicated methods. The derivative, [Ph-C≡C-PPh3]Br is capable of inhibiting the growth of tumor cells and has been shown crystallographically to have a significant interaction with the DnaK protein. Thus, solid state structures for all seven phosphonium salts prepared have been reported as they may be of interest to others in this field. Sterically encoumbered phosphines such as Mes3P did not react with Ph-C≡C-Br, however (2,4,6-MeO-C6H2)3P was found to slowly react at moderate temperature to give the expected alkynyl phosphonium salt. However at higher temperatures, the alkynyl phosphonium undergoes an intramolecular cyclizaiton to form a phosphonium analogue of a 1,4-oxazine. Finally, electronic strucutre calculations reveal the positive charge on the acetylenic β-carbon; a result of the a significant contribution of other canonical structures. The flexibilty of the P-C≡C bond has been investigated showing a low-engergy barrier (The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author