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1.
Emerg Microbes Infect ; 11(1): 168-171, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1623181

ABSTRACT

HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.


Subject(s)
Common Cold/epidemiology , Coronavirus Infections/epidemiology , Coronavirus OC43, Human/genetics , Genome, Viral , Genotype , Pneumonia, Viral/epidemiology , Base Sequence , Bayes Theorem , Child , Child, Hospitalized , Child, Preschool , China/epidemiology , Common Cold/pathology , Common Cold/transmission , Common Cold/virology , Coronavirus Infections/pathology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Coronavirus OC43, Human/classification , Coronavirus OC43, Human/pathogenicity , Epidemiological Monitoring , Female , Humans , Infant , Male , Monte Carlo Method , Mutation , Phylogeny , Pneumonia, Viral/pathology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Recombination, Genetic
2.
Cell Discov ; 7(1): 65, 2021 Aug 12.
Article in English | MEDLINE | ID: covidwho-1569241

ABSTRACT

The current COVID-19 pandemic, caused by SARS-CoV-2, poses a serious public health threat. Effective therapeutic and prophylactic treatments are urgently needed. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS-CoV-2, which binds to the receptor binding domain (RBD) of SARS-CoV-2 spike protein. Here, we developed recombinant human ACE2-Fc fusion protein (hACE2-Fc) and a hACE2-Fc mutant with reduced catalytic activity. hACE2-Fc and the hACE2-Fc mutant both efficiently blocked entry of SARS-CoV-2, SARS-CoV, and HCoV-NL63 into hACE2-expressing cells and inhibited SARS-CoV-2 S protein-mediated cell-cell fusion. hACE2-Fc also neutralized various SARS-CoV-2 strains with enhanced infectivity including D614G and V367F mutations, as well as the emerging SARS-CoV-2 variants, B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.1 (Kappa), and B.1.617.2 (Delta), demonstrating its potent and broad-spectrum antiviral effects. In addition, hACE2-Fc proteins protected HBE from SARS-CoV-2 infection. Unlike RBD-targeting neutralizing antibodies, hACE2-Fc treatment did not induce the development of escape mutants. Furthermore, both prophylactic and therapeutic hACE2-Fc treatments effectively protected mice from SARS-CoV-2 infection, as determined by reduced viral replication, weight loss, histological changes, and inflammation in the lungs. The protection provided by hACE2 showed obvious dose-dependent efficacy in vivo. Pharmacokinetic data indicated that hACE2-Fc has a relative long half-life in vivo compared to soluble ACE2, which makes it an excellent candidate for prophylaxis and therapy for COVID-19 as well as for SARS-CoV and HCoV-NL63 infections.

3.
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
4.
J. Jilin Univ. Med. Ed. ; 3(46): 625-629, 20200501.
Article in Chinese | ELSEVIER | ID: covidwho-727532

ABSTRACT

Objective: To investigate the effect of modified fecal drainage device on avoiding the occupational exposure infection of the medical staffs in the treatment of corona virus disease 2019 (COVID-19), and to provide the reference for the clinical treatment of COVID-19 and avoiding the occupational exposure infection of the medical staffs. Methods: The clinical data of a critical COVID-19 patient with diarrhea as the main symptom were collected. The modified fecal drainage device of F18 silicone gastric tube connected with disposable negative pressure drainage device was uesd to treat the fecal excrement of the patient. The general data of the medical staffs, containing 16 doctors and 48 nurses∗ were collected. The COVID-19 serological antibodies and pharyngeal swabs of the medical staffs were tested every 2 weeks. Results: The 78-year-old woman patient was admitted to hospital due to diarrhea∗ cough and expectoration for 15 d, chest distress and shortness of breath for 10 d» and fever for 1 d. The test result of COVID-19 pharyngeal swabs of the patient was positive. After the feces were collected with the modified fecal drainage device, the average operation time of medical staffs was reduced from 20 min to 10 min, the patient's perianal skin flushing subsided, and no incontinence-associated dermatitis ( IAD ) occurred. The patient was cured but remained in hospital for the other underlying diseases. The test results of COVID-19 serological antibodies and pharyngeal swabs of 64 medical staffs were all negative, all the medical staffs had no infection. Conclusion: The modified fecal drainage device has better stability, which can effectively prevent IAD and the spread of COVID-19 and reduce the risk of occupational exposure infection of medical staffs, and it is suitable for clinical promotion application.

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