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.

Purpose To perform MRI examination after the death of SD rat model due to cerebral infarction and to investigate the changing characteristics of cerebral infarction during postmortem examination. Materials and Methods Middle cerebral artery occlusion (MCAO) model was established on 21 SD rats by applying modified suture method. 13 to 56 h after modeling, 12 dead SD rats were collected for the experiment. The bodies were stored at an environment with a temperature of 10-15°C and relative humidity of 45%-55%. Head MRI was performed 12 h after modeling and at 8, 24, 48, 72 and 96 h after death respectively, and apparent diffusion coefficient (ADC) values of infarction and contralateral brain tissue were calculated. At each post-mortem time point, ADC values of bilateral cerebral hemispheres, ADC values of infarction and living infarction, and ADC values of non-infarcted brain and living non-infarcted zone were compared. Brain tissue was taken after scan for pathological diagnosis and compared with diagnostic results of postmortem MRI (pmMRI). Results The right cerebral signal of rats was abnormal 12 h after cerebral infarction and after death. Eight rats were found to have shifted cerebral middle-line structure to the left. ADC values of infarction at each time point after death were lower than that of non-infarction, the difference of which was statistically significant (P<0.05); ADC values of infarction were lower than that of living infarction, the difference of which was statistically significant (P<0.05); ADC value of non-infarcted area at each time point was lower than that of living non-infarcted area, the difference of which was statistically significant (P<0.05). Necrosis and disintegration of neurons, disintegration and liquefaction of glial fibers, infiltration of inflammatory cells and leakage of red blood cells were spotted in necrotic areas after receiving cerebral HE staining in rat. HE staining was consistent with the infarction zone indicated by pmMRI. Conclusion pmMRI can be used for the diagnosis of cerebral infarction via virtual necropsy.