Octyl gallate targeting the 3C-like protease exhibits highly efficient antiviral activity against swine enteric coronavirus PEDV.

Infection with porcine epidemic diarrhea virus (PEDV) causes severe watery diarrhea in newborn piglets, leading to substantial financial losses for the swine industry. In this study, we screened small molecule drugs targeting 3 C-like protease (3CLpro) by molecular docking, and further evaluated the antiviral activity of the screened drugs against PEDV. Results showed that octyl gallate (OG), a widely used food additive, exhibited strong binding affinity with the 3CLpro active sites of PEDV. Bio-layer interferometry and fluorescence resonance energy transfer revealed that OG directly interacts with PEDV 3CLpro (KD = 549 nM) and inhibits 3CLpro activity (IC50 = 22.15 µM). OG showed a strong inhibition of PEDV replication in vitro. Virus titers were decreased by 0.58 and 0.71 log10 TCID50/mL for the CV777 and HM2017 strains, respectively. In vivo, all piglets in the PEDV-infected group died at 48 h post-infection (hpi), while 75% of piglets in the OG treatment group showed significant relief from the clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Moreover, the western blotting results showed that OG also has strong antiviral activity against other swine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV). Our findings revealed that OG could be developed as a novel antiviral drug against PEDV. The OG exhibited a potential broad-spectrum antiviral drug for control of other swine enteric coronaviruses.

Impact of the COVID-19 Pandemic on Elective Surgery for Colorectal Cancer.

PURPOSE: To investigate the impact of the COVID-19 pandemic on patients with colorectal cancer undergoing elective surgery. METHODS: The medical records of patients with colorectal cancer who underwent elective surgery in our department during the COVID-19 pandemic (February 1 to May 31, 2020) were collected and analyzed. We compared the clinical data with colorectal cancer during the same 4-month period in 2018 and 2019. RESULTS: Sixty-seven patients with colorectal cancer underwent elective surgery during the COVID-19 pandemic. This was 66% of the number of patients that underwent the procedure during the same period in 2018 and 2019. During the COVID-19 pandemic, the proportion of patients without any digestive system symptoms decreased to 3% and severe clinical symptoms decreased by 20.9%. The proportion of right colon cancer decreased by 17.9%, while the proportion of rectal cancer increased by 52.2%, as compared with 2018 and 2019. The fraction of protective stoma was significantly higher than in 2018 (23.9% vs. 8.7%, p = 0.011). Compared with 2019, the average post-operative stay was significantly shorter than in 2018 (9.6 ± 3.7 vs. 12.1 ± 9.1, p = 0.015). Compared with 2019, the number of patients with perineural invasion (a feature of adverse prognosis) significantly increased (p = 0.009). CONCLUSION: During the COVID-19 pandemic, the number of patients undergoing elective surgery for colorectal cancer was reduced. However, the tumor stage of patients did not change substantially. We suggest that the clinical diagnosis and treatment of colorectal cancer should strictly comply with national and professional standards.

Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator.

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.