The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.

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In the recent outbreak of COVID-19, many countries have taken various kinds of quarantine measures to slow down the explosive spreading of COVID-19. Although these measures were proven to be successful in stopping the outbreak in China, the potential adverse effects of countrywide quarantine have not been thoroughly investigated. In this study, we performed an online survey to evaluate the psychological effects of quarantine in China using Zung Self-rating Anxiety Scale in February 2020 when the outbreak was nearly peaked in China. Along with the anxiety scores, limited personal information such as age, gender, region, education, occupation and specifically, the type and duration of quarantine were collected for analysis. For a total number of 992 valid questionnaires, clinical significance of anxiety symptoms was observed in 9.58% respondents according to clinical diagnostic standards in China. Statistical results showed population with different age, education level, health status and personnel category responded differently. Other characteristics such as gender, marital status, region, and acquaintance with suspected or confirmed cases of COVID-19 did not affect anxiety levels significantly. Respondents experienced different forms of quarantine showed different anxiety levels. Unexpectedly, longer durations of quarantine did not lead to significant increase of anxiety level. Our results suggest a rather mild negative psychological influence caused by the countrywide quarantine during COVID-19 outbreak in China and provided reference for other countries and regions to battle COVID-19.