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The SARS-CoV-2 coronavirus encodes an essential papain-like protease domain as part of its non-structural protein (nsp)-3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin-like ISG15 protein modifications as well as, with lower activity, Lys48-linked polyubiquitin. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin-binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. To identify PLpro inhibitors in a repurposing approach, screening of 3,727 unique approved drugs and clinical compounds against SARS2 PLpro identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, noncovalent small molecule SARS PLpro inhibitors also target SARS2 PLpro, prevent self-processing of nsp3 in cells and display high potency and excellent antiviral activity in a SARS-CoV-2 infection model.

Program, 1990;Mitchell et al., 1999). Mitchell et al. (1999) also reported a perceived decline in soil qualityThe high-value, large-scale crop production systems in the San among producers. As a result of these concerns, many Joaquin Valley (SJV) of California typically entail intensive tillage and large fertilizer and water inputs but few C additions to the soil.SJV producers have begun to question the long-term Such practices often contribute to a decline in soil quality. Our objec-sustainability of their intensively managed agricultural tive for this participatory study was to examine the effects of supplesystems. mental C management practices (SCMPs) on various soil quality To help farmers in the SJV evaluate the soil quality indicators. To increase farmer participation, we conducted the study effects of alternative soil management practices, the West on farms using a variety of SCMPs, including cover crops, compost and Side On-Farm Demonstration Project (WSD) was conmanure amendments, and several different crop rotations common ducted from 1995 to 1998. This participatory research to the region. The SCMPs significantly changed a number of soil and extension program originally included 11 large-scale properties, including soil organic matter (SOM); total Kjeldahl N; SJV row-crop producers, University of California Coopmicrobial biomass C and N; exchangeable K; Olsen P; and extractable erative Extension researchers, USDA Natural Resources Fe, Mn, and Zn. A comparison including previously established, adjacent organic, conventional, and transitional fields in addition to the Conservation Service (NRCS) conservationists, USDAtreatment fields at one farm revealed significant differences in 16 of ARS scientists, and private-sector consultants. soil quality indicators. A soil quality index computed for this farmDeveloping science-based guidelines to quantify imscored the established organic system significantly higher than the pacts of routinely used organic inputs in this region was conventional system. Our results suggest that significant changes in identified as an important priority among the project's several soil quality indicators occur with a variety of SCMPs. This is farmer participants (Mitchell and Goodell, 1996). A especially noteworthy considering the intensive tillage, irrigation, and brief, written survey of 15 participants, conducted durhot, semiarid environment of the SJV, California, where increases in ing a routine project meeting, invited input about their SOM and related soil properties are generally not expected in a 3-yr

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