SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis.

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.

The relationship between gut microbiota and COVID-19 progression: new insights into immunopathogenesis and treatment.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a global health crisis. Increasing evidence underlines the key role of competent immune responses in resisting SARS-CoV-2 infection and manifests the disastrous consequence of host immune dysregulation. Elucidating the mechanisms responsible for deregulated host immunity in COVID-19 may provide a theoretical basis for further research on new treatment modalities. Gut microbiota comprises trillions of microorganisms colonizing the human gastrointestinal tract and has a vital role in immune homeostasis and the gut-lung crosstalk. Particularly, SARS-CoV-2 infection can lead to the disruption of gut microbiota equilibrium, a condition called gut dysbiosis. Due to its regulatory effect on host immunity, gut microbiota has recently received considerable attention in the field of SARS-CoV-2 immunopathology. Imbalanced gut microbiota can fuel COVID-19 progression through production of bioactive metabolites, intestinal metabolism, enhancement of the cytokine storm, exaggeration of inflammation, regulation of adaptive immunity and other aspects. In this review, we provide an overview of the alterations in gut microbiota in COVID-19 patients, and their effects on individuals' susceptibility to viral infection and COVID-19 progression. Moreover, we summarize currently available data on the critical role of the bidirectional regulation between intestinal microbes and host immunity in SARS-CoV-2-induced pathology, and highlight the immunomodulatory mechanisms of gut microbiota contributing to COVID-19 pathogenesis. In addition, we discuss the therapeutic benefits and future perspectives of microbiota-targeted interventions including faecal microbiota transplantation (FMT), bacteriotherapy and traditional Chinese medicine (TCM) in COVID-19 treatment.

Electrochemical Biosensors Based on Carbon Nanomaterials for Diagnosis of Human Respiratory Diseases.

In recent years, respiratory diseases have increasingly become a global concern, largely due to the outbreak of Coronavirus Disease 2019 (COVID-19). This inevitably causes great attention to be given to the development of highly efficient and minimal or non-invasive methods for the diagnosis of respiratory diseases. And electrochemical biosensors based on carbon nanomaterials show great potential in fulfilling the requirement, not only because of the superior performance of electrochemical analysis, but also given the excellent properties of the carbon nanomaterials. In this paper, we review the most recent advances in research, development and applications of electrochemical biosensors based on the use of carbon nanomaterials for diagnosis of human respiratory diseases in the last 10 years. We first briefly introduce the characteristics of several common human respiratory diseases, including influenza, COVID-19, pulmonary fibrosis, tuberculosis and lung cancer. Then, we describe the working principles and fabrication of various electrochemical biosensors based on carbon nanomaterials used for diagnosis of these respiratory diseases. Finally, we summarize the advantages, challenges, and future perspectives for the currently available electrochemical biosensors based on carbon nanomaterials for detecting human respiratory diseases.

Immunogenicity, durability, and safety of an mRNA and three platform-based COVID-19 vaccines as a third dose following two doses of CoronaVac in China: A randomised, double-blinded, placebo-controlled, phase 2 trial.

Background: More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods: This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 µg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 µg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 µg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings: Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation: Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding: Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

Retrospective study of the immunogenicity and safety of the CoronaVac SARS-CoV-2 vaccine in people with underlying medical conditions.

BACKGROUND: People living with chronic disease, particularly seniors (≥60 years old), made up of most severe symptom and death cases among SARS-CoV-2 infected patients. However, they are lagging behind in the national COVID-19 vaccination campaign in China due to the uncertainty of vaccine safety and effectiveness. Safety and immunogenicity data of COVID-19 vaccines in people with underlying medical conditions are needed to address the vaccine hesitation in this population. METHODS: We included participants (≥40 years old) who received two doses of CoronaVac inactivated vaccines (at a 3-5 week interval) and were healthy or had at least one of 6 common chronic diseases. The incidence of adverse events after vaccination was monitored. Vaccine immunogenicity was studied by determining neutralizing antibodies and SARS-CoV-2-specific T cell responses post vaccination. RESULTS: Here we show that chronic diseases are associated with a higher rate of mild fatigue following the first dose of CoronaVac. By day 14-28 post vaccination, the neutralizing antibody level shows no significant difference between disease groups and healthy controls, except for people with coronary artery disease (p = 0.0287) and chronic respiratory disease (p = 0.0416), who show moderate reductions. Such differences diminish by day 90 and 180. Most people show detectable SARS-CoV-2-specific T cell responses at day 90 and day 180 without significant differences between disease groups and healthy controls. CONCLUSIONS: Our results highlight the comparable safety, immunogenicity and cellular immunity memory of CoronaVac in seniors and people living with chronic diseases. This data should reduce vaccine hesitancy in this population.

People living with chronic diseases, particularly those over the age of 60, are more likely to have severe symptoms and die following SARS-CoV-2 infection. However, many have not been vaccinated during the national COVID-19 vaccination campaign in China due to concerns about vaccine safety and effectiveness. Here we show that the inactivated COVID-19 vaccine, CoronaVac, is as safe in older people with chronic diseases as it is for healthy people. Also, only slightly differences are seen in the immune response of people with diseases compared to healthy people. Overall, our results highlight that the CoronaVac vaccine is safe and effective in people living with chronic diseases.

A soluble DR5-Fc chimeric protein attenuates inflammatory responses induced by coronavirus MHV-A59 and SARS-CoV-2.

Mortality in coronavirus disease 2019 (COVID-19) patients has been linked to the presence of a "cytokine storm" induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which involves elevated levels of circulating cytokines and immune-cell hyperactivation. Targeting cytokines during the management of COVID-19 patients has the potential to improve survival rates and reduce mortality. Although cytokine blockers and immune-host modulators are currently being tested in severely ill COVID-19 patients to cope with the overwhelming systemic inflammation, there is not too many successful cases, thus finding new cytokine blockers to attenuate the cytokine storm syndrome is meaningful. In this paper, we significantly attenuated the inflammatory responses induced by mouse hepatitis viruses A59 and SARS-CoV-2 through a soluble DR5-Fc (sDR5-Fc) chimeric protein that blocked the TNF-related apoptosis-inducing ligand-death receptor 5 (TRAIL-DR5) interaction. Our findings indicates that blocking the TRAIL-DR5 pathway through the sDR5-Fc chimeric protein is a promising strategy to treat COVID-19 severe patients requiring intensive care unit  admission or with chronic metabolic diseases.

Evidence of Infection of Human Embryonic Stem Cells by SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially described to target the respiratory system and now has been reported to infect a variety of cell types, including cardiomyocytes, neurons, hepatocytes, and gut enterocytes. However, it remains unclear whether the virus can directly infect human embryonic stem cells (hESCs) or early embryos. Herein, we sought to investigate this question in a cell-culture system of hESCs. Both the RNA and S protein of SARS-CoV-2 were detected in the infected hESCs and the formation of syncytium was observed. The increased level of subgenomic viral RNA and the presence of dsRNA indicate active replication of SARS-CoV-2 in hESCs. The increase of viral titers in the supernatants revealed virion release, further indicating the successful life cycle of SARS-CoV-2 in hESCs. Remarkably, immunofluorescence microscopy showed that only a small portion of hESCs were infected, which may reflect low expression of SARS-CoV-2 receptors. By setting |log2 (fold change)| > 0.5 as the threshold, a total of 1,566 genes were differentially expressed in SARS-CoV-2-infected hESCs, among which 17 interferon-stimulated genes (ISGs) were significantly upregulated. Altogether, our results provide novel evidence to support the ability of SARS-CoV-2 to infect and replicate in hESCs.

Management strategies and outcomes of acute coronary syndrome (ACS) during Covid-19 pandemic.

BACKGROUND: The COVID-19 outbreak represents a significant challenge to international health. Several studies have reported a substantial decrease in the number of patients attending emergency departments with acute coronary syndromes (ACS) and there has been a concomitant rise in early mortality or complications during the COVID-19 pandemic. A modified management system that emphasizes nearby treatment, safety, and protection, alongside a closer and more effective multiple discipline collaborative team was developed by our Chest Pain Center at an early stage of the pandemic. It was therefore necessary to evaluate whether the newly adopted management strategies improved the clinical outcomes of ACS patients in the early stages of the COVID-19 pandemic. METHODS: Patients admitted to our Chest Pain Center from January 25th to April 30th, 2020 based on electronic data in the hospitals ACS registry, were included in the COVID-19 group. Patients admitted during the same period (25 January to 30 April) in 2019 were included in the pre-COVID-19 group. The characteristics and clinical outcomes of the ACS patients in the COVID-19 period group were compared with those of the ACS patients in the pre-COVID-19 group. Multivariate logistic regression analyses were used to identify the risk factors associated with clinical outcomes. RESULTS: The number of patients presenting to the Chest Pain Center was reduced by 45% (p = 0.01) in the COVID-19 group, a total of 223 ACS patients were included in the analysis. There was a longer average delay from the onset of symptom to first medical contact (FMC) (1176.9 min vs. 625.2 min, p = 0.001) in the COVID-19 period group compared to the pre-COVID-19 group. Moreover, immediate percutaneous coronary intervention (PCI) (80.1% vs. 92.3%, p = 0.008) was performed less frequently on ACS patients in the COVID-19 group compared to the pre-COVID-19 group. However, more ACS patients received thrombolytic therapy (5.8% vs. 0.6%, p = 0.0052) in the COVID-19 group than observed in the pre-COVID-19 group. Interestingly, clinical outcome did not worsen in the COVID-19 group when cardiogenic shock, sustained ventricular tachycardia, ventricular fibrillation or use of mechanical circulatory support (MCS) were compared against the pre-COVID-19 group (13.5% vs. 11.6%, p = 0.55). Only age was independently associated with composite clinical outcomes (HR = 1.3; 95% CI 1.12-1.50, p = 0.003). CONCLUSION: This retrospective study showed that the adverse outcomes were not different during the COVID-19 pandemic compared to historical control data, suggesting that newly adopted management strategies might provide optimal care for ACS patients. Larger sample sizes and longer follow-up periods on this issue are needed in the future.

The adenosine analog prodrug ATV006 is orally bioavailable and has preclinical efficacy against parental SARS-CoV-2 and variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus driving the ongoing coronavirus disease 2019 (COVID-19) pandemic, continues to rapidly evolve. Because of the limited efficacy of vaccination in prevention of SARS-CoV-2 transmission and continuous emergence of variants of concern (VOCs), orally bioavailable and broadly efficacious antiviral drugs are urgently needed. Previously, we showed that the parent nucleoside of remdesivir, GS-441524, has potent anti-SARS-CoV-2 activity. Here, we report that esterification of the 5'-hydroxyl moieties of GS-441524 markedly improved antiviral potency. This 5'-hydroxyl-isobutyryl prodrug, ATV006, demonstrated excellent oral bioavailability in rats and cynomolgus monkeys and exhibited potent antiviral efficacy against different SARS-CoV-2 VOCs in vitro and in three mouse models. Oral administration of ATV006 reduced viral loads and alleviated lung damage when administered prophylactically and therapeutically to K18-hACE2 mice challenged with the Delta variant of SARS-CoV-2. These data indicate that ATV006 represents a promising oral antiviral drug candidate for SARS-CoV-2.

Prevention and Control of COVID-19 after Resuming General Hospital Functions.

During the COVID-19 pandemic, many general hospitals have been transformed into designated infectious disease care facilities, where a large number of patients with COVID-19 infections have been treated and discharged. With declines in the number of hospitalizations, a major question for our healthcare systems, especially for these designated facilities, is how to safely resume hospital function after these patients have been discharged. Here, we take a designated COVID-19-care facility in Wuhan, China, as an example to share our experience in resuming hospital function while ensuring the safety of patients and medical workers. After more than 1200 patients with COVID-19 infections were discharged in late March, 2020, our hospital resumed function by setting up a three-level hospital infection management system with four grades of risk of exposure. Moreover, we also took measures to ensure the safety of medical personnel in different departments including clinics, wards, and operation rooms. After all patients with COVID-19 infections were discharged, during the five months of regular function from April to September in 2020, no positive cases have been found among more than 40,000 people in our hospital, including hospital staff and patients.

Comparison of model-specific histopathology in mouse models of COVID-19.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS-CoV-2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock-in strains, and viral vector-mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS-CoV-2 are unknown. Here, we perform systematic comparisons of the mouse models including K18-hACE2 mice, KI-hACE2 mice, Ad5-hACE2 mice and CAG-hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS-CoV-2 researches. The similarities or differences among the model-specific pathologies may help in better understanding the pathogenic process of SARS-CoV-2 infection and aiding in the development of effective medications and prophylactic treatments for SARS-CoV-2.

The Impact of Accumulated Mutations in SARS-CoV-2 Variants on the qPCR Detection Efficiency.

SARS-CoV-2 is evolving with mutations throughout the genome all the time and a number of major variants emerged, including several variants of concern (VOC), such as Delta and Omicron variants. In this study, we demonstrated that mutations in the regions corresponding to the sequences of the probes and 3'-end of primers have a significant impact on qPCR detection efficiency. We also found that the G28916T mutation of the N gene accounts for 78.78% sequenced genomes of Delta variant. It was found that detection sensitivity of G28916T mutant was 2.35 and 1.74 times less than that of the wt sequence and detection limit was reduced from 1 copy/µl to 10 copies/µl for the commercially available CP3 and CP4 primer/probe sets. These results indicate that the detection probes and primers should be optimized to keep maximal detection efficiency in response to the emergence of new variants.

E-learners' satisfaction as predictors of online classroom community

Purpose: This study investigates Chinese college students' satisfaction with using e-learning systems and its influences on their sense of online classroom community in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format during the COVID-19 pandemic. Methods: A total number of 307 college students were recruited with 270 usable responses from a southeastern university in China. E-learner satisfaction measurement and Classroom Community Scale (both with a 5-point Likert-type scale) were used as the instruments to investigate the research questions. Descriptive statistical analysis and multiple regression analysis were conducted in SPSS. Results: Results of the analysis show that Chinese college students' satisfaction of using the e-learning system regarding the learner interface, learning community, content, and personalization positively impacts their sense of online classroom community no matter in synchronous, asynchronous, or a blend of both synchronous and asynchronous online course format. Implications: A well-developed e-learning system would enhance students' sense of online classroom community. Specifically, the user interface, interaction, content arrangement, and personalization should be focused on when developing the e-learning system.

Prediction of in-hospital recurrence and false-negative results in patients with COVID-19 by red blood cell values on admission.

The clinical characteristics and risk factors of patients with coronavirus disease 2019 (COVID-19) with re-positive or false-negative test results have so far remained to be determined. The present study provides a cross-sectional observational study on 134 hospitalized patients selected from Huoshenshan Hospital (Wuhan, China) using cluster sampling. A total of 68 patients had reduced red blood cell (RBC) counts, 55 a decrease in the hemoglobin concentration (HBC) and 73 a decline in hematocrit (HCT). The false-negative rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA detection in pharyngeal swab specimens was 18.7%. The absolute lymphocyte count (ALC), RBC, HBC and HCT levels in false-negative patients were significantly higher than those in patients who tested positive for viral nucleic acids. Multivariate logistic regression analysis indicated that RBC [odds ratio (OR)=0.43, 95% CI: 0.18-0.99], HBC (OR=0.97, 95% CI: 0.94-0.99) and ALC (OR=0.43, 95% CI: 0.20-0.91) were the factors influencing the negative testing results for viral nucleic acid. The rate of re-positive patients was 16.4%. The white blood cell, RBC, HBC and HCT values in re-positive patients were lower than those in non-re-positive patients. The median (interquartile range) values for RBC, HBC and HCT of male re-positive patients were 3.95 (3.37, 4.2) x1012/l, 123 (103, 133) g/l and 36.6 (31.1, 39.2)%, respectively, while the RBC, HBC and HCT of female re-positive patients were 3.54 (3.13, 3.74) x1012/l, 115 (102, 118) g/l and 34.2 (28.5, 34.9)%, respectively. It was determined that RBC, HBC and HCT values had moderate accuracy in predicting SARS-CoV-2 recurrence in patients with COVID-19 using receiver operating curve analysis. The present study suggested that RBC may have an important role in the pathogenesis of COVID-19.

Independent Risk Factors for the Dynamic Development of COVID-19: A Retrospective Study.

OBJECTIVE: To identify the risk factors for predicting the dynamic progression of COVID-19. METHODS: A total of 2321 eligible patients were included in this study from February 4 to April 15, 2020. Two illness conditions, including mild/moderate (M/M) subtype to severe/critical (S/C) and S/C to fatality, were classified. Clinical message was collected and compared, respectively. Kaplan-Meier method, Cox regression model and risk score system were used to predict disease progression in S/C COVID-19. RESULTS: A total of 112 of 1761 patients with M/M subtype were progressors (P) and 1649 non-progressors (NP). Increasing disease progression associated with higher levels of neutrophils count (HR=1.958, 95% CI=1.253-3.059, P=0.003), CK (HR=2.203, 95% CI=1.048-4.632, P=0.037), LDH (HR=3.309, 95% CI=2.083-5.256, P<0.001) and CRP (HR=2.575, 95% CI=1.638-4.049, P<0.001), and lower level of lymphocytes count (HR=1.549, 95% CI=1.018-2.355, P=0.041), as well as total lesion volume ratio greater than ≥10% (HR=2.286, 95% CI=1.451-3.601, P<0.001) on admission. In progression to fatality, 56 of the 672 S/C cases died and 616 survived. Increasing fatality associated with lower level of lymphocytes count (HR:2.060, 95% CI:1.000-4.242, P=0.050), higher levels of BUN (HR:2.715, 95% CI:1.539-4.790, P<0.001), CK-MB (HR:3.412, 95% CI:1.760-6.616, P<0.001), LDH (HR:5.578, 95% CI:2.317-13.427, P<0.001), and PT (HR:3.619, 95% CI:2.102-6.231, P<0.001). Furthermore, high risk of neutrophils count, lymphocytes count, CK, LDH, CRP, and total lesion volume ratio was powerfully correlated with the incidence of progression to S/C in patients with NS COVID-19 and high odds of lymphocytes count, BUN, CK-MB, LDH, and PT were significantly associated with death in patients with S/C COVID-19. In addition, the progression and mortality rates increased with increasing risk scores. CONCLUSION: Elevated LDH level and lymphopenia were independent predictors for COVID-19 sustainable management in classifying non-severe patients who progressed to severe condition and identifying S/C patients who deteriorated to fatal outcomes as well. Total lesion volume ratio ≥10% may provide early predictive evidence with COVID-19 patients at high risk of developing into S/C to improve prognosis.

Considerations and perspectives on digestive diseases during the COVID-19 pandemic: a narrative review.

Coronavirus disease 2019 (COVID-19) was initially reported in December 2019, and since then it has become a pandemic with newly confirmed cases and deaths increasing continuously. The COVID-19 pandemic has dramatically impacted the organization and execution of activities in the clinical sector. Asymptomatic infections are increasingly being identified when patients seek medical advice for non-respiratory system illnesses, particularly digestive system symptoms. This has posed a significant challenge for clinical diagnosis and treatment. Based on the clinical symptoms of patients with COVID-19 reported to date, patients with typical clinical symptoms of COVID-19 may also present with symptoms associated with the digestive system. Digestive illness symptoms in patients with COVID-19 are underscored by a bidirectional relationship between respiratory and digestive systems. Because the clinical diagnosis and treatment of digestive illnesses caused by COVID-19 have been challenging so far, we hypothesized that investigating the pathogenesis of digestive system diseases in patients with COVID-19 will provide potential novel targets for its prevention and treatment, and concurrently reduce COVID-19 virulence and socio-sanitary burden. This review summarizes the relationship between the digestive and respiratory systems in patients with COVID-19 from the perspective of the "gut-lung" axis. We discuss extant literature on the pathogenesis of COVID-19-related digestive symptoms, which may facilitate differential diagnosis and treatment of this condition.

Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro.

COVID-19 has become a global pandemic and there is an urgent call for developing drugs against the virus (SARS-CoV-2). The 3C-like protease (3CLpro) of SARS-CoV-2 is a preferred target for broad spectrum anti-coronavirus drug discovery. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CLpro activity in vitro with IC50's of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC50's of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CLpro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CLpro, demonstrating their potential as broad-spectrum anti-coronavirus drugs.

Potent inhibitors of SARS-CoV-2 3C-like protease derived from N-substituted isatin compounds.

SARS-CoV-2 3C-like protease is the main protease of SARS-CoV-2 and has been considered as one of the key targets for drug discovery against COVID-19. We identified several N-substituted isatin compounds as potent SARS-CoV-2 3C-like protease inhibitors. The three most potent compounds inhibit SARS-CoV-2 3C-like protease with IC50's of 45 nM, 47 nM and 53 nM, respectively. Our study indicates that N-substituted isatin compounds have the potential to be developed as broad-spectrum anti-coronavirus drugs.