Geraniin as a potential inhibitor of SARS-CoV-2 3CLpro.

Geraniin is a polyphenolic compound first isolated from Geranium thunbergii. The major protease (Mpro), namely 3 C-like protease (3CLpro), of coronaviruses is considered an attractive drug target as it is essential for the processing and maturation of viral polyproteins. Thus, our primary goal is to explore the efficiency of geraniin on 3CLpro of SARS-CoV-2 using the computational biology strategy. In this work, we studied the anti-coronavirus effect of geraniin in vitro and its potential inhibitory mode against the 3CLpro of SARS-CoV-2. We found that geraniin inhibited HCoV-OC43 coronavirus-infected cells during the attachment and penetration phases. Molecular docking and dynamics simulations exhibited that geraniin had a strong binding affinity and high stable binding to 3CLpro of SARS-CoV-2. Geraniin showed a strong inhibitory activity on coronavirus and may be a potential inhibitor of SARS-CoV-2 3CLpro.

Timing of endoscopic intervention in patients with cirrhosis with acute variceal haemorrhage (TEACH trial): protocol for a randomised clinical trial (RCT).

INTRODUCTION: Acute variceal haemorrhage (AVH) in patients with cirrhosis remains a topic of great interest. Although several guidelines recommend endoscopy within 24 hours after AVH, there is no consensus on the most appropriate time to perform this intervention. The purpose of this study is to identify whether urgent endoscopy (within 6 hours after gastroenterological consultation) is superior to non-urgent endoscopy (between 6 hours and 24 hours after gastroenterological consultation) in reducing the rebleeding rate of these patients. METHODS AND ANALYSIS: This is a single-centred, prospective, randomised clinical trial. Between March 2021 and December 2023, an estimated 400 patients will be randomised in a 1:1 ratio to receive endoscopic intervention either within 6 hours or between 6 and 24 hours after gastroenterological consultation. Randomisation will be conducted by permuted block randomisation, with stratification by age, systolic blood pressure and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of AVH. The secondary efficacy endpoints mainly include all-cause mortality within 42 days after randomisation, persistent bleeding, length of hospitalisation, etc. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethical Committees of Jinling Hospital (authorised ethics no. DZQH-KYLL-21-01). This trial will provide valuable insights into the timing of endoscopic intervention for AVH in patients with cirrhosis. Furthermore, the trial results and conclusions could provide high-quality evidence to guide clinical research and treatment. TRIAL REGISTRATION NUMBER: NCT04786743.

Epidemiological profile of a cluster of COVID-19 caused by an imported case

Objective: To understand the epidemiological characteristics of a cluster of COVID-19 caused by an imported case in late December 2020, and to provide reference for the prevention and control of COVID-19.

Significant reduced traffic in Beijing failed to relieve haze pollution during the COVID-19 lockdown: implications for haze mitigation (preprint)

The COVID-19 outbreak greatly limited human activities and reduced primary emissions particularly from urban on-road vehicles, but coincided with Beijing experiencing pandemic haze, raising the public concerns of the validity and effectiveness of the imposed traffic policies to improve the air pollution. Here, we explored the relationship between local vehicle emissions and the winter haze in Beijing before and during the COVID-19 lockdown period based on an integrated analysis framework, which combines a real-time on-road emission inventory, in-situ air quality observations and a localized chemical transport modeling system. We found that traffic emissions decreased substantially affected by the pandemic, with a higher reduction for NOx (75.9%, 125.3 Mg/day) compared to VOCs (53.1%, 52.9 Mg/day). Unexpectedly, our results show that the imbalanced emission abatement of NOx and VOCs from vehicles led to a significant rise of the atmospheric oxidizing capacity in urban areas, but only resulting in modest increases in secondary aerosols due to the inadequate precursors. However, the enhanced oxidizing capacity in the surrounding regions greatly increased the secondary particles with relatively abundant precursors, which is mainly responsible for Beijing haze during the lockdown period. Our results indicate that the winter haze in Beijing was insensitive to the local vehicular emissions reduction due to the complicated nonlinear response of the fine particle and air pollutant emissions. We suggest mitigation policies should focus on accelerating VOC and NH3 emissions reduction and synchronously controlling regional sources to release the benefits on local traffic emission control.

Forecasting the Cumulative Number of COVID-19 Deaths in China: Can More Lives Be Saved? (preprint)

The COVID-19 outbreak is on-going in China. Here we estimated the potential total numbers of COVID-19 deaths in China, outside Hubei (in China), Hubei Province, Wuhan City and outside Wuhan (in Hubei) by Boltzmann function-based analyses, which are 3342 (95% CI, 3214, 3527), 111 (109, 114), 3245 (3100, 3423), 2613 (2498, 2767) and 627 (603, 654), respectively. The results may help to evaluate the severity of COVID-19 outbreaks and facilitate timely mental service for the families of passed patients.

Simulating and Forecasting the Cumulative Confirmed Cases of SARS-CoV-2 in China by Boltzmann Function-based Regression Analyses (preprint)

An ongoing outbreak of atypical pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is hitting Wuhan City and has spread to other provinces/cities of China and overseas. It very urgent to forecast the future course of the outbreak. Here, we provide an estimate of the potential total number of confirmed cases in mainland China by applying Boltzmann-function based regression analyses. We found that the cumulative number of confirmed cases from Jan 21 to Feb 14, 2020 for mainland China, Hubei Province, Wuhan City and other provinces were all well fitted with the Boltzmann function (R2 being close to 0.999). The potential total number of confirmed cases in the above geographic regions were estimated at 95% confidence interval (CI) as 79589 (71576, 93855), 64817 (58223, 77895), 46562 (40812, 57678) and 13956 (12748, 16092), respectively. Notably, our results suggest that the number of daily new confirmed cases of SARS-CoV-2 in mainland China (including Hubei Province) will become minimal between Feb 28 and Mar 10, 2020, with 95% CI. In addition, we found that the data of cumulative confirmed cases of 2003 SARS-CoV in China and Worldwide were also well fitted to the Boltzmann function. To our knowledge this is the first study revealing that the Boltzmann function is suitable to simulate epidemics. The estimated potential total number of confirmed cases and key dates for the SARS-CoV-2 outbreak may provide certain guidance for governments, organizations and citizens to optimize preparedness and response efforts.