Nitazoxanide and JIB-04 have broad-spectrum antiviral activity and inhibit SARS-CoV-2 replication in cell culture and coronavirus pathogenesis in a pig model

Pathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50 of 695 nM, with a specificity index of greater than 1,000. JIB-04 showed in vitro antiviral activity in multiple cell types against several DNA and RNA viruses, including porcine coronavirus transmissible gastroenteritis virus. In an in vivo porcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved weight gain and survival. These results highlight the potential utility of JIB-04 as an antiviral agent against SARS-CoV-2 and other viral pathogens.

Simulation of the spatial and temporal changes of complex non-point source loads in a lake watershed of central China.

In this study, a coupling model of agricultural and urban non-point source (AUNPS) is established in order to estimate complex non-point source (NPS) pollutant loads in the urban-rural fringe. Furthermore, a spatial-temporal change model of non-point source (CA-AUNPS) is established by the coupling of AUNPS and cellular automata (CA) models. The total nitrogen (TN) and total phosphorus (TP) loads in Tangxun watershed were simulated during 1991-2020, and the results show that: (1) the CA-AUNPS model is an effective tool to simulate the spatial-temporal changes of NPS pollutant loads in urban-rural fringe; (2) in terms of the spatial changes, the TN and TP loads generally showed as rural/urban construction land > farmland > forest/green land, and the high-value areas of NPS pollutant loads expanded from north to south with the increase of construction land; with regard to temporal changes, the TN and TP loads generally displayed an increasing tendency during 1991-2020, and by 2020 the TN and TP loads will increase to 370.06 and 33.89 t yr(-1), respectively; (3) the spatial-temporal changes of TN and TP loads in Tangxun watershed correlate strongly with the land-use, slope, and rainfall.