Polyphyllin I Effects Candida albicans via Inhibition of Virulence Factors.

Paris polyphylla is often used in Chinese medicine to treat conditions such as carbuncles, trauma, snake bites, and mosquito bites. In the present study, we investigated the effect and mechanism of the morphological transition and extracellular phospholipase activity of Candida albicans treated with polyphyllin I (PPI). First, the minimum inhibitory concentration and antifungal activity of PPI were evaluated using the multiple microdilution method and time-killing assays. Then, the effect of PPI on the morphological transition of Candida albicans in Spider liquid medium and Sabouraud-dextrose liquid medium containing 10% fetal bovine serum was observed under an inverted microscope and by scanning electron microscopy. Finally, egg yolk agar plates were used to evaluate extracellular phospholipase activity. Gene expression was detected by real-time quantitative polymerase chain reaction analysis. Our results suggest that PPI inhibited the transition from the yeast to the hyphal stage and decreased secreted aspartyl proteinase activity. We further confirmed that PPI significantly downregulated the expression of extracellular phospholipase genes and cAMP-PKA signaling pathway-related genes. Taken together, our results suggest that PPI exerts anti-Candida albicans activity by inhibiting virulence characteristics, including the yeast-to-hyphal transition and the secretion of aspartyl proteases and phospholipases. The study results also indicated that PPI could be a promising therapeutic strategy for Candida albicans.

Laboratory predictors of severe Coronavirus Disease 2019 and lung function in followed-up.

BACKGROUND: A pandemic caused by SARS-CoV-2 has infected more than 79 million people and killed exceeding 1.7 million people around the world by the end of 2020. METHOD: We obtained the clinical data of all diagnosed patients and lung function test of followed-up patients in Fuyang, Anhui province to investigate laboratory predictors of severe Coronavirus Disease 2019 (COVID-19) and the impairment of lung function. RESULTS: Of the 155 patients, 87 (56.13%) were males. The mean age was 41.95 (SD 15.34) years. Only 30 (19.35%) patients had the critical condition. Fever (84.52%) was the most common symptoms, and short of breath was more common in severe patients (p < 0.01). Lymphopenia was observed in most patients (74, 47.7%). It showed the elevation of CRP in 100 (64.5%) patients, the elevation of SAA or IL-6 in 104 (67.1%) patients. The calculated cut-off value of CRP was 19.35 mg/ml, the AUC was 0.777, sensitivity was 73.3%, specificity was 69.6%; SAA was 73.55 mg/L, 0.679, 83.3%, 56.8%, respectively; IL-6 was 18.85 pg/ml, 0.797, 83.3%, 64.8%; D-Dimer was 0.325 mg/L, 0.673, 66.7% and 68.8%. The combination of CRP, SAA, IL-6, and D-Dimer was 0.823 in AUC, 73.3% in sensitivity, and 78.4% in specificity. 12 (42.86%) followed-up patients had completely normal lung function indicators. CONCLUSION: Elevated CRP, SAA, IL-6 and D-Dimer can be predictors to severe COVID-19. The combination of these four indicators can improve the effectivity and specificity of assessing severe COVID-19. Most of the followed-up patients showed no abnormalities in lung function test. Abnormal lung function is mainly reflected in the diffusion function.

Screening potential FDA-approved inhibitors of the SARS-CoV-2 major protease 3CLpro through high-throughput virtual screening and molecular dynamics simulation.

It has been confirmed that the new coronavirus SARS-CoV-2 caused the global pandemic of coronavirus disease 2019 (COVID-19). Studies have found that 3-chymotrypsin-like protease (3CLpro) is an essential enzyme for virus replication, and could be used as a potential target to inhibit SARS-CoV-2. In this work, 3CLpro was used as the target to complete the high-throughput virtual screening of the FDA-approved drugs, and Indinavir and other 10 drugs with high docking scores for 3CLpro were obtained. Studies on the binding pattern of 3CLpro and Indinavir found that Indinavir could form the stable hydrogen bond (H-bond) interactions with the catalytic dyad residues His41-Cys145. Binding free energy study found that Indinavir had high binding affinity with 3CLpro. Subsequently, molecular dynamics simulations were performed on the 3CLpro and 3CLpro-Indinavir systems, respectively. The post-dynamic analyses showed that the conformational state of the 3CLpro-Indinavir system transformed significantly and the system tended to be more stable. Moreover, analyses of the residue interaction network (RIN) and H-bond occupancy revealed that the residue-residue interaction at the catalytic site of 3CLpro was significantly enhanced after binding with Indinavir, which in turn inactivated the protein. In short, through this research, we hope to provide more valuable clues against COVID-19.

Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in Fuyang, Anhui, China.

OBJECTIVE: To investigate the epidemiological and clinical features of patients with COVID-19 in Anhui province of China. METHOD: In this descriptive study, we obtained epidemiological, demographic, manifestations, laboratory data and radiological findings of patients confirmed by real-time RT-PCR in the NO.2 People's Hospital of Fuyang City from Jan 20 to Feb 9, 2020. Clinical outcomes were followed up to Feb 18, 2020. RESULTS: Of 125 patients infected SARS-CoV-2, the mean age was 38.76 years (SD, 13.799) and 71(56.8%) were male. Common symptoms include fever [116 (92.8%)], cough [102(81.6%)], and shortness of breath [57(45.6%)]. Lymphocytopenia developed in 48(38.4%) patients. 100(80.0%) patients showed bilateral pneumonia, 26(20.8%) patients showed multiple mottling and ground-glass opacity. All patients were given antiviral therapy. 19(15.2%) patients were transferred to the intensive care unit. By February 18, 47(37.6%) patients were discharged and none of patients died. Among the discharged patients, the median time of length of stay was 14.8 days (SD 4.16). CONCLUSION: In this single-center, retrospective, descriptive study, fever is the most common symptom. Old age, chronic underlying diseases and smoking history may be risk factors to worse condition. Certain laboratory inspection may contribute to the judgment of the severity of illness.