ACP-Dnnel: Anti-coronavirus Peptides Prediction based on Deep Neural Network Ensemble Learning (preprint)

Background The ongoing COVID-19 pandemic has caused global economic crisis and dramatic loss of human life. There is an urgent need for safe and efficient anti-coronavirus infection drugs. Anti-coronavirus peptides (ACovPs) can inhibit coronavirus infection. With high-efficiency, low-toxicity, and broad-spectrum inhibitory effects on coronaviruses, they are promising candidates to be developed into a new type of anti-coronavirus drug. Experiment is the traditional way of ACovPs identification, which is less efficient and more expensive. With the accumulation of experimental data on ACovPs, computational prediction provides a cheaper and faster way to find anti-coronavirus peptides candidates.Methods In this study, we integrated several state-of-the-art machine learning methodologies to build nine classification models for the prediction of ACovPs. These models were pretrained using deep neural networks, and the performance of our ensemble model, ACP-Dnnel, was evaluated across three datasets and independent dataset.Results The highest accuracy of ACP-Dnnel reaches 98%, and the MCC value exceeds 0.9. On three different datasets, its average accuracy is 96.33%. After the latest independent data set validation, ACP-Dnnel improved at MCC, Sn and ACC values by 10.1%, 16.4% and 7.3% respectively. It is suggested that ACP-Dnnel can be helpful for the laboratory identification of ACovPs, speeding up the anti-coronavirus peptide drug discovery and development. We constructed the web server of anti-coronavirus peptides prediction and it is available at http://150.158.148.228:5000/.

Ultrasensitive detection of SARS-CoV-2 S protein with aptamers biosensor based on surface-enhanced Raman scattering.

A rapid and accurate diagnostic modality is essential to prevent the spread of SARS-CoV-2. In this study, we proposed a SARS-CoV-2 detection sensor based on surface-enhanced Raman scattering (SERS) to achieve rapid and ultrasensitive detection. The sensor utilized spike protein deoxyribonucleic acid aptamers with strong affinity as the recognition entity to achieve high specificity. The spherical cocktail aptamers-gold nanoparticles (SCAP) SERS substrate was used as the base and Au nanoparticles modified with the Raman reporter molecule that resonates with the excitation light and spike protein aptamers were used as the SERS nanoprobe. The SCAP substrate and SERS nanoprobes were used to target and capture the SARS-CoV-2 S protein to form a sandwich structure on the Au film substrate, which can generate ultra-strong "hot spots" to achieve ultrasensitive detection. Analysis of SARS-CoV-2 S protein was performed by monitoring changes in SERS peak intensity on a SCAP SERS substrate-based detection platform. This assay detects S protein with a LOD of less than 0.7 fg mL-1 and pseudovirus as low as 0.8 TU mL-1 in about 12 min. The results of the simulated oropharyngeal swab system in this study indicated the possibility of it being used for clinical detection, providing a potential option for rapid and accurate diagnosis and more effective control of SARS-CoV-2 transmission.

The Cytoplasmic Domain of the SARS-CoV-2 Envelope Protein Assembles into a ß-Sheet Bundle in Lipid Bilayers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein forms a pentameric ion channel in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment (ERGIC) of the infected cell. The cytoplasmic domain of E interacts with host proteins to cause virus pathogenicity and may also mediate virus assembly and budding. To understand the structural basis of these functions, here we investigate the conformation and dynamics of an E protein construct (residues 8-65) that encompasses the transmembrane domain and the majority of the cytoplasmic domain using solid-state NMR. 13C and 15N chemical shifts indicate that the cytoplasmic domain adopts a ß-sheet-rich conformation that contains three ß-strands separated by turns. The five subunits associate into an umbrella-shaped bundle that is attached to the transmembrane helices by a disordered loop. Water-edited NMR spectra indicate that the third ß-strand at the C terminus of the protein is well hydrated, indicating that it is at the surface of the ß-bundle. The structure of the cytoplasmic domain cannot be uniquely determined from the inter-residue correlations obtained here due to ambiguities in distinguishing intermolecular and intramolecular contacts for a compact pentameric assembly of this small domain. Instead, we present four structural topologies that are consistent with the measured inter-residue contacts. These data indicate that the cytoplasmic domain of the SARS-CoV-2 E protein has a strong propensity to adopt ß-sheet conformations when the protein is present at high concentrations in lipid bilayers. The equilibrium between the ß-strand conformation and the previously reported α-helical conformation may underlie the multiple functions of E in the host cell and in the virion.

Liver chemistries in severe or non-severe cases of COVID-19: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) patients exhibit different patterns of liver impairment, according to growing evidence. AIM: In this study, we sought to provide a comprehensive analysis of liver test parameters in patients with severe and non-severe COVID-19. METHODS: We performed a meta-analysis of published liver manifestations and described the liver damage in COVID-19. We searched PubMed, Google Scholar, Embase, Cochrane Library, medRxiv, bioRxiv, and three Chinese electronic databases through April 18, 2020, in accordance with the Preferred Reporting Items for Meta-Analyses. We analyzed pooled data on liver chemistries stratified by COVID-19 severity using a fixed or random-effects model. RESULTS: A meta-analysis of 56 studies, including 11052 patients, found that the pooled mean alanine aminotransferase (ALT) in severe COVID-19 cases was 35.9 IU/L whereas in non-severe COVID-19 cases was 27.3 IU/L. Average aspartate aminotransferase (AST) levels were 44.3 IU/L in severe cases compared to 27.9 IU/L in non-severe cases. In addition, AST levels are often higher than ALT levels regardless of disease severity. The severe cases tended to have a higher gamma-glutamyltransferase level but a lower albumin level than the non-severe cases. CONCLUSION: Severe COVID-19 was more likely to be associated with abnormal liver test results. Monitoring liver chemistry closely can help detect disease progression early.

Air pollution and CO2 emission inventory of Chinese civil aviation airport

Based on the aircraft take-off and landing data of the Civil Aviation Administration of China,fleet configuration data,and the ICAO aircraft engine emission factor database from 2017 to 2020,the air pollution and CO2 emission inventory of the landing and take-off（LTO） cycle of high-resolution aircraft of civil aviation airport of China were developed from bottom to top.On this basis,the spatial and temporal distribution characteristics of air pollutants and CO2 on air pollution of China Civil Aviation Airport LTO cycle were explored.We analyzed the 3epidemics from 2000 to 2020（SARS in 2003,MERS in 2012,and COVID-19 in 2020）on airport air pollution and CO2 emissions.The results show that the emissions of NOx,CO,HC,SO2,PM,and CO2 in the LTO cycle of civil aviation airports in China in 2020 are 10.90,8.22,0.96,0.28,0.06,1360.27 million tons respectively;The emissions of HC,CO,SO2,and CO2 are the largest in the taxiing stage,accounting for 92.80%,91.56%,41.81% and 41.81% of the total emissions respectively.The emissions of NOx and PM are the largest in the climbing stage,accounting for 47.93% and 37.39% of the total emissions respectively;Air pollutants and CO2 emissions from China's Civil Aviation Airport LTO cycle showed an increasing trend over the past 2017～2019 years,and the total emissions in 2020 were reduced by 22.39% by COVID-19.The most concentrated emission area is the economically developed East region.In the 3 epidemics of the 2000～2020 years,COVID-19 has the most significant impact on the LTO emissions from China's civil aviation airport.

SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers.

The SARS-CoV-2 envelope (E) protein is a viroporin associated with the acute respiratory symptoms of COVID-19. E forms cation-selective ion channels that assemble in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment. The channel activity of E is linked to the inflammatory response of the host cell to the virus. Like many viroporins, E is thought to oligomerize with a well-defined stoichiometry. However, attempts to determine the E stoichiometry have led to inconclusive results and suggested mixtures of oligomers whose exact nature might vary with the detergent used. Here, we employ 19F solid-state nuclear magnetic resonance and the centerband-only detection of exchange (CODEX) technique to determine the oligomeric number of E's transmembrane domain (ETM) in lipid bilayers. The CODEX equilibrium value, which corresponds to the inverse of the oligomeric number, indicates that ETM assembles into pentamers in lipid bilayers, without any detectable fraction of low-molecular-weight oligomers. Unexpectedly, at high peptide concentrations and in the presence of the lipid phosphatidylinositol, the CODEX data indicate that more than five 19F spins are within a detectable distance of about 2 nm, suggesting that the ETM pentamers cluster in the lipid bilayer. Monte Carlo simulations that take into account peptide-peptide and peptide-lipid interactions yielded pentamer clusters that reproduced the CODEX data. This supramolecular organization is likely important for E-mediated virus assembly and budding and for the channel function of the protein.

Different clinical features of children and adults in regional outbreak of Delta COVID-19.

BACKGROUND: This study compared clinical features of the Delta variant of coronavirus disease 2019 (COVID-19) in children and adults. METHODS: Clinical data included 80 children and 132 adults with the Delta variant of COVID-19, hospitalized in the Affiliated Hospital of Putian College between September and October 2021. The data was analyzed retrospectively. RESULTS: The proportion of mild patients in the children group (50%) was higher than that in the adults group (17.9%). Cough (25%, 20/80) and diarrhea (1.3%, 1/80) symptoms in children group were significantly less frequent. Compared with adults, there was no significant difference in the viral load of SARS-CoV-2 in samples collected by nasopharyngeal swabs. In children, lymphocyte count was higher [1.98 (0.25-4.25) vs 1.20 (0.29-4.27) ×109/L], whereas the interleukin-6 level was lower [5.87 (1.50-61.40) vs 15.15 (1.79-166.30) pg/mL] than that in adults group. Additionally, the incidence of liver injury in children group was lower than that in adults group. There was no significant difference in the incidence of proteinuria (22/75 vs 45/112) between the two groups, but the serum creatinine level in children was lower [42.0 (28.0-73.0) vs 57.0 (32.0-94.0) µmol/L]. CONCLUSION: Compared with adults, children with the Delta variant of COVID-19 have differences in symptoms, clinical classification, inflammatory indices, and liver/kidney function injury. Children's illness is relatively mild. Clinicians should pay attention to their differences and use drugs accurately.

Fear of Progression, Anxiety, and Depression in Patients With Advanced Melanoma in the COVID-19 and Post-COVID-19 Era.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic causes great disruption to cancer care services, which might bring about psychological problems and further lower both physical and mental life quality in cancer patients. Until now, very few studies focused on the psychological distress of patients with advanced melanoma before or during the epidemic. This study aimed to elucidate the fear of progression (FoP), anxiety, depression, and related independent predictors in patients with advanced melanoma during the COVID-19 outbreak. Methods: Two hundred and seventy-three patients with unresectable stage III or metastatic melanoma were recruited from February 2020 to November 2021, and completed the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), State Trait Anxiety Inventory (STAI-6), and Patient Health Questionnaire (PHQ-9). Results: One hundred and seventy-four (64.7%) patients experienced heighted FoP (FoP-Q-SF: 39.9 ± 11.0), 198 (72.5%) patients reported elevated anxiety (STAI-6: 13.1 ± 3.0), and 62 (22.7%) patients had increased depression (PHQ-9: 6.4 ± 6.1). In multivariate analysis, illness duration (OR = 0.987 for FoP; OR = 0.984 for depression), cancer stage (OR = 14.394 for anxiety) and disease progression (OR = 1.960 for FoP; OR = 23.235 for anxiety; OR = 1.930 for depression) were independent predictors for FoP, anxiety or depression. Additionally, the high levels of FoP, anxiety and depression were significantly positive correlated with each other (r = 0.466 for FoP and anxiety; r = 0.382 for FoP and depression; r = 0.309 for anxiety and depression). Conclusion: Our study indicates that FoP, anxiety and depression are persisting among patients with advanced melanoma in the COVID-19 and post-COVID-19 era. Effective psycho-oncological interventions are needed for melanoma patients with psychological distress during the ongoing COVID-19 pandemic.

Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients: A Retrospective Observational Study.

OBJECTIVE: To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older. METHODS: This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression. RESULTS: Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19. CONCLUSION: The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

COVID-19 and liver dysfunction: What nutritionists need to know.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

Potential role of vitamin D in patients with diabetes, dyslipidaemia, and COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 has become a worldwide public health crisis. Studies have demonstrated that diabetes and dyslipidaemia are common comorbidities and could be high-risk factors for severe COVID-19. Vitamin D, a group of fat-soluble compounds responsible for intestinal absorption of calcium, magnesium, and phosphate, has been widely used as a dietary supplement for the prevention and treatment of numerous diseases, including infectious and non-infectious diseases, due to its high cost-effectiveness; safety; tolerability; and anti-thrombotic, anti-inflammatory, antiviral, and immunomodulatory properties. In this letter to the editor, we mainly discuss the potential role of vitamin D in patients with diabetes, dyslipidaemia, and COVID-19.

pH- and Calcium-Dependent Aromatic Network in the SARS-CoV-2 Envelope Protein.

The envelope (E) protein of the SARS-CoV-2 virus is a membrane-bound viroporin that conducts cations across the endoplasmic reticulum Golgi intermediate compartment (ERGIC) membrane of the host cell to cause virus pathogenicity. The structure of the closed state of the E transmembrane (TM) domain, ETM, was recently determined using solid-state NMR spectroscopy. However, how the channel pore opens to mediate cation transport is unclear. Here, we use 13C and 19F solid-state NMR spectroscopy to investigate the conformation and dynamics of ETM at acidic pH and in the presence of calcium ions, which mimic the ERGIC and lysosomal environment experienced by the E protein in the cell. Acidic pH and calcium ions increased the conformational disorder of the N- and C-terminal residues and also increased the water accessibility of the protein, indicating that the pore lumen has become more spacious. ETM contains three regularly spaced phenylalanine (Phe) residues in the center of the peptide. 19F NMR spectra of para-fluorinated Phe20 and Phe26 indicate that both residues exhibit two sidechain conformations, which coexist within each channel. These two Phe conformations differ in their water accessibility, lipid contact, and dynamics. Channel opening by acidic pH and Ca2+ increases the population of the dynamic lipid-facing conformation. These results suggest an intricate aromatic network that regulates the opening of the ETM channel pore. This aromatic network may be a target for E inhibitors against SARS-CoV-2 and related coronaviruses.

Network-Based Approach to Repurpose Approved Drugs for COVID-19 by Integrating GWAS and Text Mining Data

The coronavirus disease 19 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has a rapidly increasing prevalence and has caused significant morbidity/mortality. Despite the availability of many vaccines that can offer widespread immunization, it is also important to reach effective treatment for COVID-19 patients. However, the development of novel drug therapeutics is usually a time-consuming and costly process, and therefore, repositioning drugs that were previously approved for other purposes could have a major impact on the fight against COVID-19. Here, we first identified lung-specific gene regulatory/interaction subnetworks (COVID-19-related genes modules) enriched for COVID-19-associated genes obtained from GWAS and text mining. We then screened the targets of 220 approved drugs from DrugBank, obtained their drug-induced gene expression profiles in the LINCS database, and constructed lung-specific drug-related gene modules. By applying an integrated network-based approach to quantify the interactions of the COVID-19-related gene modules and drug-related gene modules, we prioritized 13 approved drugs (e.g., alitretinoin, clocortolone, terazosin, doconexent, and pergolide) that could potentially be repurposed for the treatment of COVID-19. These findings provide important and timely insights into alternative therapeutic options that should be further explored as COVID-19 continues to spread.

Measuring the impact of an exogenous factor: An exponential smoothing model of the response of shipping to COVID-19.

Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19.

Clinical features of Chinese children with COVID-19 and other viral respiratory infections.

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.

Outcomes of atrial fibrillation in patients with COVID-19 pneumonia: A systematic review and meta-analysis.

BACKGROUND: Recently, emerging evidence has suggested that atrial fibrillation (AF) has an epidemiological correlation with coronavirus disease 2019 (COVID-19). However, the clinical outcomes of AF in COVID-19 remain inconsistent and inconclusive. The aim of this study was to provide a comprehensive description of the impact of AF on the prognosis of patients with COVID-19 pneumonia. METHODS: Three electronic databases (PubMed, Embase, and Web of Science) were searched for eligible studies as of March 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations between AF (preexisting and new-onset) and in-hospital mortality, post-discharge mortality, and ventilator use. RESULTS: A total of 36 individual studies were incorporated into our meta-analysis. The combined results revealed that preexisting AF was associated with increased in-hospital mortality (pooled OR: 2.07; 95% CI: 1.60-2.67; p < 0.001), post-discharge mortality (pooled OR: 2.69; 95% CI: 1.24-5.83; p < 0.05), and ventilator utilization (pooled OR: 4.53; 95% CI: 1.33-15.38; p < 0.05) in patients with COVID-19. In addition, our data demonstrated that new-onset AF during severe acute respiratory syndrome coronavirus 2 infection was significantly correlated with increased mortality (pooled OR: 2.38; 95% CI: 2.04-2.77; p < 0.001). CONCLUSIONS: The presence of AF is correlated with adverse outcomes in patients with COVID-19 pneumonia, which deserves increased attention and should be managed appropriately to prevent adverse outcomes.

Structure and drug binding of the SARS-CoV-2 envelope protein transmembrane domain in lipid bilayers.

An essential protein of the SARS-CoV-2 virus, the envelope protein E, forms a homopentameric cation channel that is important for virus pathogenicity. Here we report a 2.1-Å structure and the drug-binding site of E's transmembrane domain (ETM), determined using solid-state NMR spectroscopy. In lipid bilayers that mimic the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane, ETM forms a five-helix bundle surrounding a narrow pore. The protein deviates from the ideal α-helical geometry due to three phenylalanine residues, which stack within each helix and between helices. Together with valine and leucine interdigitation, these cause a dehydrated pore compared with the viroporins of influenza viruses and HIV. Hexamethylene amiloride binds the polar amino-terminal lumen, whereas acidic pH affects the carboxy-terminal conformation. Thus, the N- and C-terminal halves of this bipartite channel may interact with other viral and host proteins semi-independently. The structure sets the stage for designing E inhibitors as antiviral drugs.