Functionalized protein microparticles targeting hACE2 as a novel preventive strategy for SARS-CoV-2 infection.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), resulting in a serious burden on public health and social economy worldwide. SARS-CoV-2 infection is mainly initialized in the nasopharyngeal cavity through the binding of viral spike (S) protein to human angiotensin-converting enzyme 2 (hACE2) receptors which are widely expressed in many human cells. Thus, blockade of the interaction between viral S protein and hACE2 receptor in the primary entry site is a promising prevention strategy for the management of COVID-19. Here we showed protein microparticles (PMPs) decorated with hACE2 could bind and neutralize SARS-CoV-2 S protein-expressing pseudovirus (PSV) and protect host cells from infection in vitro. In the hACE2 transgenic mouse model, administration of intranasal spray with hACE2-decorated PMPs markedly decreased the viral load of SARS-CoV-2 in the lungs though the inflammation was not attenuated significantly. Our results provided evidence for developing functionalized PMPs as a potential strategy for preventing emerging air-borne infectious pathogens, such as SARS-CoV-2 infection.

Detection of RNA-dependent RNA polymerase of porcine epidemic diarrhea virus.

The RNA synthesis of porcine epidemic diarrhea virus (PEDV) is a sophisticated process performed by a multilingual viral replication complex, together with cellular factors. A key enzyme of this replication complex is RNA-dependent RNA polymerase (RdRp). However, there is limited knowledge about PEDV RdRp. In our present study, a polyclonal antibody against RdRp was prepared by using a prokaryotic expression vector pET-28a-RdRp to study the function of PEDV RdRp and provide a tool to investigate PEDV pathogenesis. In addition, the enzyme activity and half-life of PEDV RdRp were investigated. The result showed that the polyclonal antibody against PEDV RdRp was successfully prepared and was able to be used to detect PEDV RdRp by immunofluorescence and western blotting. Additionally, enzyme activity of PEDV RdRp reached nearly 2 pmol/µg/h and the half-life of PEDV RdRp was 5.47 h.

Thickness-Sensing Sandwiched Plasmonic Biosensors Enable Label-Free Naked-Eye Antibody Quantification.

Clinical serology assays for detecting the antibodies of the virus are time-consuming, are less sensitive/selective, or rely on sophisticated detection instruments. Here, we develop a sandwiched plasmonic biosensor (SPB) for supersensitive thickness-sensing via utilizing the distance-dependent electromagnetic coupling in sandwiched plasmonic nanostructures. SPBs quantitatively amplify the thickness changes on the nanoscale range (sensitivity: ∼2% nm-1) into macroscopically visible signals, thereby enabling the rapid, label-free, and naked-eye detection of targeted biomolecular species (via the thickness change caused by immunobinding events). As a proof of concept, this assay affords a broad dynamic range (7 orders of magnitude) and a low LOD (∼0.3 pM), allowing for the extremely accurate SARS-CoV-2 antibody quantification (sensitivity/specificity: 100%/∼99%, with a portable optical fiber device). This strategy is suitable for high-throughput multiplexed detection and smartphone-based sensing at the point-of-care, which can be expanded for various sensing applications beyond the fields of viral infections and vaccination.

Changes in Temporal Properties of Notifiable Infectious Disease Epidemics in China During the COVID-19 Pandemic: Population-Based Surveillance Study.

BACKGROUND: COVID-19 was first reported in 2019, and the Chinese government immediately carried out stringent and effective control measures in response to the epidemic. OBJECTIVE: Nonpharmaceutical interventions (NPIs) may have impacted incidences of other infectious diseases as well. Potential explanations underlying this reduction, however, are not clear. Hence, in this study, we aim to study the influence of the COVID-19 prevention policies on other infectious diseases (mainly class B infectious diseases) in China. METHODS: Time series data sets between 2017 and 2021 for 23 notifiable infectious diseases were extracted from public data sets from the National Health Commission of the People's Republic of China. Several indices (peak and trough amplitudes, infection selectivity, preferred time to outbreak, oscillatory strength) of each infectious disease were calculated before and after the COVID-19 outbreak. RESULTS: We found that the prevention and control policies for COVID-19 had a strong, significant reduction effect on outbreaks of other infectious diseases. A clear event-related trough (ERT) was observed after the outbreak of COVID-19 under the strict control policies, and its decreasing amplitude is related to the infection selectivity and preferred outbreak time of the disease before COVID-19. We also calculated the oscillatory strength before and after the COVID-19 outbreak and found that it was significantly stronger before the COVID-19 outbreak and does not correlate with the trough amplitude. CONCLUSIONS: Our results directly demonstrate that prevention policies for COVID-19 have immediate additional benefits for controlling most class B infectious diseases, and several factors (infection selectivity, preferred outbreak time) may have contributed to the reduction in outbreaks. This study may guide the implementation of nonpharmaceutical interventions to control a wider range of infectious diseases.

Is there association of olanzapine and pulmonary embolism: A case report

Olanzapine is a second‐generation antipsychotic drug that is often used to treat schizophrenia and manic attacks. An increasing number of cases in recent years have shown that olanzapine is associated with vascular thromboembolic disease (VTD). Here, we reported a case of patient with history of taking aripiprazole, benzhexol, olanzapine, and sertraline for 5 years. He was admitted because of aggravated chest tightness, chest pain, and shortness of breath sustaining for 3 days. Laboratory examination and computed tomography angiography of the chest revealed new pulmonary embolus which involved the main trunk of the pulmonary artery and bilateral pulmonary arteries, with pneumonic infiltration in the left upper lobe. After thrombolytic therapy, the patient was out of danger. This case report described a 36‐year‐old man who developed pulmonary embolism with 5 years' oral antipsychotic drugs. 3 days before being admitted, he was vaccinated with COVID‐19 vaccine. He had risk factor of smoking, obesity, and hyperlipidemia for VTD.

Fetal neurodevelopmental spatio-temporal dynamic transcriptional landscape of maternal insult-induce autism spectrum disorder risk.

Maternal insults during pregnancy induces an increased risk of autism spectrum disorders (ASD) in offspring, but the neuropathological changes in this process remains not to be established. To shed light on this, the transcriptome datasets of maternal blood samples with children later diagnosed with ASD and typical development, and tissue samples of multiple brain regions from ASD patients and human neurodevelopment were conducted to identify the non-chasm differentially expressed genes (DEGs) to generate the spatio-temporal dynamic change. Combined enrichment and interaction network analysis revealed that non-chasm DEGs with similar expression trajectories in the same brain regions, were involved in neural, immune and metabolic GO functions and KEGG pathways, respectively, suggesting that did not performed exactly the same functions. Interestingly, our results found that non-chasm DEGs in frontal cortex and temporal cortex were associated with COVID-19, suggesting that as an environmental risk factor COVID-19 affects an increased risk of ASD.

Clinical characteristics, laboratory abnormalities and CT findings of COVID-19 patients and risk factors of severe disease: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is an emerging pandemic of global public health concern. We aimed to summarize the characteristics of COVID-19 patients in the early stage of the pandemic and explore the risk factors of disease progression. METHODS: We conducted a systematic review with meta-analysis, searching three databases for studies published between January 1, 2020, and March 18, 2020. We used random-effects models to calculate the 95% confidence intervals of pooled estimated prevalence and the odds ratio between the severe and nonsevere cases. RESULTS: Ninety studies involving 16,526 COVID-19 patients were included. Hypertension (19.1%) and diabetes (9.5%) were the most common comorbidities. The most prevalent clinical symptoms were fever (78.4%), cough (58.5%), and fatigue (26.4%). Increased serum ferritin (74.2%), high C-reactive protein (73.3%), and high erythrocyte sedimentation rate (ESR) (72.2%) were the most frequently reported laboratory abnormalities. Most patients had bilateral lung involvement (82.2%) and showed peripheral (66.9%) and subpleural (62.1%) distribution, with multifocal involvement (73.1%). And the most common CT features were vascular enlargement (64.3%), ground-glass opacity (GGO) (60.7%), and thickened interlobular septa (55.1%). Respiratory failure was the most common complication (30.7%) and the overall case-fatality rate (CFR) was 4.2%. Moreover, male, history of smoking, and comorbidities might influence the prognosis. Most clinical symptoms such as fever, high fever, cough, sputum production, fatigue, shortness of breath, dyspnoea, and abdominal pain were linked to the severity of disease. Some specific laboratory indicators implied the deterioration of disease, such as leucocytosis, lymphopenia, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, creatinine, creatine kinase (CK), lactic dehydrogenase (LDH), C-reactive protein, procalcitonin (PCT), and D-dimer. Besides, the risk of bilateral pneumonia, consolidation, pleural effusion, and enlarged mediastinal nodes was higher in severe cases. CONCLUSIONS: Most COVID-19 patients have fever and cough with lymphopenia and increased inflammatory indices, and the main CT feature is GGO involved bilateral lung. Patients with comorbidities and worse clinical symptoms, laboratory characteristics, and CT findings tend to have poor disease progression.

Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method.

The prevalence of a novel ß-coronavirus (SARS-CoV-2) was declared as a public health emergency of international concern on 30 January 2020 and a global pandemic on 11 March 2020 by WHO. The spike glycoprotein of SARS-CoV-2 is regarded as a key target for the development of vaccines and therapeutic antibodies. In order to develop anti-viral therapeutics for SARS-CoV-2, it is crucial to find amino acid pairs that strongly attract each other at the interface of the spike glycoprotein and the human angiotensin-converting enzyme 2 (hACE2) complex. In order to find hot spot residues, the strongly attracting amino acid pairs at the protein-protein interaction (PPI) interface, we introduce a reliable inter-residue interaction energy calculation method, FMO-DFTB3/D/PCM/3D-SPIEs. In addition to the SARS-CoV-2 spike glycoprotein/hACE2 complex, the hot spot residues of SARS-CoV-1 spike glycoprotein/hACE2 complex, SARS-CoV-1 spike glycoprotein/antibody complex, and HCoV-NL63 spike glycoprotein/hACE2 complex were obtained using the same FMO method. Following this, a 3D-SPIEs-based interaction map was constructed with hot spot residues for the hACE2/SARS-CoV-1 spike glycoprotein, hACE2/HCoV-NL63 spike glycoprotein, and hACE2/SARS-CoV-2 spike glycoprotein complexes. Finally, the three 3D-SPIEs-based interaction maps were combined and analyzed to find the consensus hot spots among the three complexes. As a result of the analysis, two hot spots were identified between hACE2 and the three spike proteins. In particular, E37, K353, G354, and D355 of the hACE2 receptor strongly interact with the spike proteins of coronaviruses. The 3D-SPIEs-based map would provide valuable information to develop anti-viral therapeutics that inhibit PPIs between the spike protein of SARS-CoV-2 and hACE2.