Isotopic #evidence for a cold and distant #origin of #3IATLAS {Comet}

 

Abstract

Interstellar objects provide the only directly observable samples of icy planetesimals formed around other stars, and can therefore provide insight into the diversity of physical and chemical conditions occurring during exoplanet formation1−3. Here we report isotopic measurements of the interstellar comet 3I/ATLAS, which reveal an elemental composition unlike any Solar System body. The water in 3I/ATLAS is enriched in deuterium, at a level of D/H = (0.98 ± 0.06)%, which is more than an order of magnitude higher than in known comets, while its range of 12C/13C ratios (141–191 for CO2 and 123–172 for CO) exceeds typical values found in the Solar System, as well as nearby interstellar clouds and protoplanetary disks. Such extreme isotopic signatures indicate formation at temperatures  ≲ 30 K in a relatively metal-poor environment. When interpreted with respect to models for Galactic chemical evolution, the carbon isotopic composition implies that 3I/ATLAS may have accreted as long ago as 12 billion years, following a period of intense, early star formation. 3I/ATLAS thus represents a preserved fragment of an ancient planetary system.

Source: 

Link: https://www.nature.com/articles/s41586-026-10771-6

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#Oseltamivir aziridines are potent #influenza #neuraminidase #inhibitors and imaging agents

 

Significance

Influenza remains a major global health threat. We introduce oseltamivir-based aziridines that unite transition-state mimicry for tight binding with aziridine-enabled covalent capture of the catalytic tyrosine. This dual function yields potent, mechanism-based neuraminidase inhibition and enables activity-based quantification of active enzyme directly in complex samples. Across N1, N2, and influenza B enzymes, selected compounds show high potency against diverse viral neuraminidases and in live virus replication assays. By combining a clinically grounded scaffold with a reactivity handle, these molecules bridge therapeutic and diagnostic needs and offer a practical platform for neuraminidase imaging and antiviral development.

Abstract

Influenza neuraminidase (NA) is a critical target for seasonal and pandemic antivirals, including the strains of current concern. Current treatments, such as Zanamivir and Oseltamivir, are limited by noncovalent binding and emerging resistance. We hypothesized that Oseltamivir aziridines would unite transition-state mimicry for tight binding, with aziridine-enabled covalent capture of the catalytic tyrosine, thereby supporting both therapy and activity-based quantification. Here, we present oseltamivir-based aziridines, inspired by cyclophellitol chemistry, that act as covalent inhibitors and activity-based probes via an N-acylaziridine warhead. Free-energy calculations, and NMR observations, indicate a 4H5 half-chair preference consistent with the NA transition state, and selected analogues inhibit multiple NA subtypes with low nanomolar binding constants. Diverse evidence establishes covalency: time-dependent inactivation, inhibitor washout, intact-mass shifts, MS/MS identification of a tyrosine adduct, and QM/MM reaction profiles, while cryoEM of N1 aligns with the proposed binding mode, revealing an elimination product. The inhibitors demonstrate formidable activity against diverse viral neuraminidases, including H5N1, and further enable imaging and quantification of active NA. With their dual therapeutic and diagnostic potential, these first-in-class inhibitors indeed benefit from transition state mimicry and covalency, and thus offer a powerful platform for antiviral development and neuraminidase imaging, addressing urgent global health needs in influenza treatment and prevention.

Source: 

Link: https://www.pnas.org/doi/10.1073/pnas.2504045123

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