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1.
Chinese Journal of Zoonoses ; 37(8):688-697, 2021.
Article in Chinese | GIM | ID: covidwho-1497431

ABSTRACT

Through bioinformatics, we systematically predicted and analyzed the structure and function of TMPRSS2, a key protease used by SARS-CoV-2 to invade host cells, thus providing a reliable reference for the research on the protein and the development of its inhibitors. We used ProtParam, Protscale, SignalP 4.0 Server, SecretomeP 2.0 server, TMHMM Server v. 2.0, SOPMA, SWISS-MODEL, MEGA-X and other software to predict the structure, function, evolution, biological processes and other aspects of the TMPRSS2 gene and protein. We comprehensively analyzed and demonstrated the results obtained with each program. TMPRSS2 protein was found to be a hydrophilic protein composed of 492 amino acids. It has a transmembrane helix structure and is a non-classical secreted protein. The expression of TMPRSS2 protein in the prostate was particularly abundant, and it has abundant post-translational modification sites. TMPRSS2 protein has a total of three superfamily conserved domains, and the amino acid sequence after the 100th position is relatively conserved. We report comprehensive prediction and analysis of the structure and function of the TMPRSS2 protein. From the perspective of bioinformatics, our results verify its characteristics as a serine protease and provide a possible mechanistic explanation for its participation in SARS-CoV-2 invasion of hosts. This work should facilitate further experiments and research related to TMPRSS2.

2.
Neural Comput Appl ; : 1-16, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1446164

ABSTRACT

COVID-19 has undergone several mutations and is still spreading in most countries now. PA has positive benefits in the prevention of COVID-19 infection and counteracting the negative physical and mental effects caused by COVID-19. However, relevant evidence has indicated a high prevalence of physical inactivity among the general population, which has worsened due to the outbreak of the pandemic, and there is a severe lack of exercise guidance and mitigation strategies to advance the knowledge and role of PA to improve physical and mental health in most countries during the epidemic. This study surveyed the effects of COVID-19 on PA in Chinese residents during the pandemic and provided important reference and evidence to inform policymakers and formulate policies and planning for health promotion and strengthening residents' PA during periods of public health emergencies. ANOVA, Kolmogorov-Smirnov, the chi-square test and Spearman correlation analysis were used for statistical analysis. A total of 14,715 participants were included. The results show that nearly 70% of Chinese residents had inadequate PA (95%CI 58.0%-82.19%) during the COVID-19 outbreak, which was more than double the global level (27.5%, 95%CI 25.0%-32.2%). The content, intensity, duration, and frequency of PA were all affected during the period of home isolation, and the types of PA may vary among different ages. The lack of physical facilities and cultural environment is the main factor affecting PA. However, there was no significant correlation between insufficient PA and the infection rate. During the period of home isolation and social distance of epidemic prevention, it is necessary to strengthen the scientific remote network monitoring and guidance for the process of PA in China.

3.
Front Psychiatry ; 12: 722448, 2021.
Article in English | MEDLINE | ID: covidwho-1399181

ABSTRACT

The COVID-19 has undergone several mutations, and caused deleterious effects on physical and mental health of people worldwide. Whilst physical exercise is known for its positive effect on enhancing immunity and reducing the negative consequences of unhealthy emotional states caused by the pandemic; there is a severe lack of psychological exercise intervention measures and mitigation strategies to advance the knowledge and role of physical exercise to improve mental health in most countries. This study surveyed the association between physical exercise and mental health burden during the COVID-19 outbreak in China to better understand the influence of different physical exercise types on reducing mental health burden during the pandemic. ANOVA, binary logistic regression, the chi-square test, and Spearman's correlation analysis were used for statistical analysis. 14,715 participants were included. The results showed that Chinese residents had several poor mental health conditions during the COVID-19 outbreak. And there was a significant positive correlation between the extent of adverse effects on mental health and provincial proportions of confirmed COVID-19 cases (r = 0.365, p < 0.05). Some main factors caused an unhealthy psychological status, including epidemic severity (62.77%, 95% CI 58.62-65.64%), prolonged home quarantine (60.84%, 95% CI 58.15-63.25%), spread of large amounts of negative information about COVID-19 in the media (50.78%, 95% CI 47.46-53.15%), limitations in daily life and social interaction (45.93%, 95%CI 42.46-47.55%), concerns about students' learning (43.13%, 95% CI 40.26-45.48%), and worries about being infected (41.13%, 95% CI 39.16-45.23%). There was a significant association between physical exercise and mental health. The largest associations were seen for home-based group entertainment exercise (i.e., family games, rope skipping, and badminton), Chinese traditional sports (i.e., Chinese martial arts, Taijiquan and Qigong), and popular sports (i.e., yoga, video dancing, sensory-motor games, and whole-body vibration), as well as durations of 30-60 min per session, frequencies of three to five times per week and a total of 120-270 min of moderate-intensity exercise weekly during the COVID-19 outbreak (p < 0.05).

4.
J Biol Chem ; 295(36): 12686-12696, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-1387615

ABSTRACT

Type II transmembrane serine proteases (TTSPs) are a group of enzymes participating in diverse biological processes. Some members of the TTSP family are implicated in viral infection. TMPRSS11A is a TTSP expressed on the surface of airway epithelial cells, which has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome coronaviruses (CoVs). In this study, we examined the mechanism underlying the activation cleavage of TMPRSS11A that converts the one-chain zymogen to a two-chain enzyme. By expression in human embryonic kidney 293, esophageal EC9706, and lung epithelial A549 and 16HBE cells, Western blotting, and site-directed mutagenesis, we found that the activation cleavage of human TMPRSS11A was mediated by autocatalysis. Moreover, we found that TMPRSS11A activation cleavage occurred before the protein reached the cell surface, as indicated by studies with trypsin digestion to remove cell surface proteins, treatment with cell organelle-disturbing agents to block intracellular protein trafficking, and analysis of a soluble form of TMPRSS11A without the transmembrane domain. We also showed that TMPRSS11A was able to cleave the SARS-CoV-2 spike protein. These results reveal an intracellular autocleavage mechanism in TMPRSS11A zymogen activation, which differs from the extracellular zymogen activation reported in other TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation.


Subject(s)
Epithelial Cells/metabolism , Membrane Proteins/metabolism , Proteolysis , Serine Proteases/metabolism , A549 Cells , Cells, Cultured , HEK293 Cells , Humans , Membrane Proteins/chemistry , Membrane Proteins/genetics , Mutation , Protein Domains , Protein Transport , Respiratory Mucosa/cytology , Serine Proteases/chemistry , Serine Proteases/genetics , Spike Glycoprotein, Coronavirus/metabolism , Trypsin/metabolism
5.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-1024074

ABSTRACT

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.


Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Blocking/chemistry , COVID-19 , Cerebral Cortex , Neurons , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/metabolism , COVID-19/pathology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Cerebral Cortex/virology , Disease Models, Animal , Female , Humans , Male , Mice , Middle Aged , Neurons/metabolism , Neurons/pathology , Neurons/virology , Organoids/metabolism , Organoids/pathology , Organoids/virology
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