Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism.

Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid and arachidonic acid metabolism pathways. PSB significantly decreased the level of 12, 13- epoxyoctadecenoic (12, 13-EpOME) and increased the level of prostaglandin E2. Interestingly, exogenous supplement of 12, 13-EpOME in HCoV-OC43-infected cells significantly stimulated HCoV-OC43 virus replication. Transcriptomic analyses showed that PSB is a negative modulator of aryl hydrocarbon receptor (AHR)/cytochrome P450 (CYP) 1A1signaling pathway and its antiviral effects can be counteracted by supplement of FICZ, a well-known AHR agonist. Integrative analyses of metabolomic and transcriptomic indicated that PSB could affect linoleic acid and arachidonic acid metabolism axis through AHR/CYP1A1 pathway. These results highlight the importance of the AHR/CYP1A1 pathway and lipid metabolism in the anti-coronavirus activity of the bioflavonoid PSB.

Sodium alginate-hydrogel coatings on extracorporeal membrane oxygenation for anticoagulation.

Thromboembolism caused by the use of extracorporeal membrane oxygenation (ECMO) remains common among patients with existing heart diseases and contributes to significant morbidity and mortality during the COVID-19 pandemic. Various surface modification strategies have been proposed, showing that the methacrylated alginate (MA-SA) hydrogel layer is transparent, which aids the observation of the thromboembolism from the inner wall of the tubing. In the combined dynamic and static blood of ECMO tubing inner surface in vitro experiments, it was also demonstrated that the adhesion of blood clots to the surface of vessels was remarkably reduced, and the MA-SA-based hydrogel coating could significantly prolong the activated partial thrombin time and block the endogenous coagulation. The favorable properties of natural polysaccharides of hydrogel coatings make them the best surface material choices to be applied for blood-contacting medical devices and significantly improve anticoagulant performance.

Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eurya chinensis（Chinese Dagang Tea）have been consumed as herbal tea for centuries in Guangdong, China, and have also been used to prevent influenza and treat colds and fevers in traditional Chinese medicine. However, there are no reports on the chemical profile and efficacy of its leaves for the treatment of fever and viral infections. MATERIALS AND METHODS: The chemical constituents of Eurya chinensis leaves were isolated and identified by phytochemical study and spectroscopic data, E. chinensis extracts and compounds were evaluated for their antiviral activities by cytopathic effect (CPE) reduction and antibody-based EC50 assay. The antiviral effect of the main component was confirmed by immunofluorescence and transmission electron microscopy. Virtual screening and docking enzyme inhibition experiments were performed to analyze the anti-coronavirus mechanisms of the compounds from E. chinensis leaves. RESULTS: In this study, we found for the first time that E. chinensis leaf extract exhibited inhibitory effects against coronaviruses HCoV-OC43 in vitro. Among 23 monomer compounds isolated from E. chinensis leaf extract, the triterpenoids (betulinic acid, α-amyrin) and the flavonoids (naringenin, eriodictyol and quercetin) showed marked antiviral activity. Microscopic optical analyses further demonstrated that betulinic acid can remove virus particles from HCoV-OC43 infected cells. Virtual screening and docking analysis towards the coronavirus in vogue revealed that betulinic acid was able to bind well to PLpro and Nsp14N7-MTase, and that the flavonoids prefer to bind with PLpro, Nsp3MES, NspP14N7-MTase, Nsp16GTA, and Nsp16SAM. The enzyme inhibition experiments demonstrated that betulinic acid (1) exhibited significant inhibition of PLpro and N7-MTase activity of SARS-CoV-2. CONCLUSION: This study proposes E. chinensis and its triterpenoids and flavonoids as promising potential treatments for coronaviruses.

COVID-19 Lockdown Increased the Risk of Preterm Birth.

Purpose: To estimate whether the city-specific lockdown in Shanghai induced by the COVID-19 pandemic affected preterm birth rates among uninfected pregnant women in different trimesters. Methods: The population-based retrospective cohort study was conducted in the International Peace Maternity and Child Health Hospital (IPMCH) in Shanghai, China. Pregnant women without COVID-19 received perinatal healthcare during lockdown (from January 24, 2020 to March 24, 2020) and non-lockdown (from January 24, 2019 to March 24, 2019) period and giving birth to a live infant at IPMCH were enrolled. 1:1 propensity score matching and Inverse probability of treatment weighting were used to evaluate preterm birth (<37 weeks), very preterm birth (<34 weeks), preterm birth with premature rupture of membranes (PROM-PTB), spontaneous preterm birth with intact membranes (S-PTB), and medically induced preterm birth (MI-PTB) between two groups. Results: 8,270 pregnant women were in the lockdown group, and 9,815 were in the non-lockdown group. Pregnant women in second trimester during lockdown had a higher risk of PTB than those during the non-lockdown period [OR: 1.43 (CI 1.01-2.02), ARD: 1.7% (CI 0.04-3.4%), p = 0.045]. Furthermore, pregnant women in third trimester during lockdown had a higher risk of PROM-PTB than those during the non-lockdown period [OR: 1.64 (CI 1.09-2.47), ARD: 0.9% (CI 0.2-1.6%), p = 0.02]; no group differences were found related to rates of VPTB, S-PTB or MI-PTB. Conclusion: In this cohort study in China, we found that there was an increased risk in preterm birth for non-infected women in COVID-19 lockdown who were in their second trimester.

Thyroid Hormone Changes in Early Pregnancy Along With the COVID-19 Pandemic.

Purpose: COVID-19 (Coronavirus Disease 2019) was first reported in December 2019 and quickly swept across China and around the world. Levels of anxiety and depression were increased among pregnant women during this infectious pandemic. Thyroid function is altered during stressful experiences, and any abnormality during early pregnancy may significantly affect fetal development and pregnancy outcomes. This study aimed to determine whether the COVID-19 pandemic induces thyroid hormone changes in early pregnant women. Methods: This study comprised two groups of pregnant women in Shanghai in their first trimester - those pregnant women before the COVID-19 outbreak from January 20, 2019, to March 31, 2019 (Group 1) and those pregnant during the COVID-19 outbreak from January 20, 2020, to March 31, 2020 (Group 2). All women were included if they had early pregnancy thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and total thyroxine (TT4) concentrations, thyroid peroxidase (TPO) antibody or thyroglobulin antibody (TgAb) available and did not have a history of thyroid diseases or received thyroid treatment before or during pregnancy. We used propensity score matching to form a cohort in which patients had similar baseline characteristics. Results: Among 3338 eligible pregnant women, 727 women in Group 1 and 727 in Group 2 had similar propensity scores and were included in the analyses. Pregnant women in Group 2 had significantly higher FT3 (5.7 vs. 5.2 pmol/L, P<0.001) and lower FT4 (12.8 vs. 13.2 pmol/L, P<0.001) concentrations compared with those in Group 1. Pregnant women in Group 2 were more likely to develop isolated hypothyroxinemia (11.6% vs. 6.9%, OR, 1.75 [95% CI, 1.20-2.53], P=0.003) than those in Group 1 but had a significantly lower risk of TgAb positivity (12.0% vs. 19.0%, OR, 0.58 [95% CI, 0.43-0.78], P<0.001). Conclusion: Pregnant women in their first trimester in Shanghai during the COVID-19 outbreak were at an increased risk of having higher FT3 concentrations, lower FT4 concentrations, and isolated hypothyroxinemia. The association between thyroid hormones, pregnancy outcomes, and the COVID-19 outbreak should be explored further.