Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Genome miniaturization drives key evolutionary innovations of adaptive traits in verte-brates,such as the flight evolution of birds.However,whether similar evolutionary processes exist in invertebrates remains poorly understood.Derived from the second-largest animal phylum,scallops are a special group of bivalve molluscs and acquire the evolutionary novelty of the swimming lifestyle,providing excellent models for investigating the coordinated genome and lifestyle evolution.Here,we show for the first time that genome sizes of scallops exhibit a generally negative correlation with loco-motion activity.To elucidate the co-evolution of genome size and swimming lifestyle,we focus on the Asian moon scallop(Amusium pleuronectes)that possesses the smallest known scallop genome while being among scallops with the highest swimming activity.Whole-genome sequencing of A.pleuronectes reveals highly conserved chromosomal macrosynteny and microsynteny,suggestive of a highly con-tracted but not degenerated genome.Genome reduction of A.pleuronectes is facilitated by significant inactivation of transposable elements,leading to reduced gene length,elevated expression of genes involved in energy-producing pathways,and decreased copy numbers and expression levels of biomineralization-related genes.Similar evolutionary changes of relevant pathways are also observed for bird genome reduction with flight evolution.The striking mimicry of genome miniaturization underlying the evolution of bird flight and scallop swimming unveils the potentially common,pivotal role of genome size fluctuation in the evolution of novel lifestyles in the animal kingdom.

In recent years,with the rapid development of the Next Generation Sequencing,the tumor heterogeneity has attracted widespread attention.It has been clear that heterogeneity in the same patient includes inter-tumor heterogeneity and intra-tumor heterogeneity.The former exists between different tumor lesions,such as primary tumor and metastatic tumor,and the latter occurs in different cancer cells.Tumor heterogeneity represents the ongoing challenge in the field of cancer treatment and brings great difficulty for the precision medicine.Therefore,it is possible to achieve accurate diagnosis and therapy for tumor patients by detecting the subclone of tumors and adjusting the treatment plan in time.