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1.
Signal Transduct Target Ther ; 7(1): 186, 2022 Jun 13.
Article in English | MEDLINE | ID: covidwho-1890154

ABSTRACT

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has dramatically influenced various aspects of the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies to prevent and treat this threatening disease. It is universally acknowledged that cell death and cell autophagy are essential and crucial to maintaining host homeostasis and participating in disease pathogenesis. At present, more than twenty different types of cell death have been discovered, some parts of which have been fully understood, whereas some of which need more investigation. Increasing studies have indicated that cell death and cell autophagy caused by coronavirus might play an important role in virus infection and pathogenicity. However, the knowledge of the interactions and related mechanisms of SARS-CoV-2 between cell death and cell autophagy lacks systematic elucidation. Therefore, in this review, we comprehensively delineate how SARS-CoV-2 manipulates diverse cell death (including apoptosis, necroptosis, pyroptosis, ferroptosis, and NETosis) and cell autophagy for itself benefits, which is simultaneously involved in the occurrence and progression of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies.


Subject(s)
COVID-19 , Apoptosis , Autophagy/genetics , Humans , Pandemics , SARS-CoV-2
2.
Cell Mol Immunol ; 19(5): 577-587, 2022 May.
Article in English | MEDLINE | ID: covidwho-1830043

ABSTRACT

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Histones , Mice , N-Acetylneuraminic Acid , Protein Subunits/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Virus Internalization
3.
Chinese Journal of Nosocomiology ; 31(19):2891-2895, 2021.
Article in Chinese | CAB Abstracts | ID: covidwho-1519490

ABSTRACT

OBJECTIVE To evaluate the implementation of normalization prevention and control measures for the COVID-2019 epidemic by quantitative assessment, and to evaluated the effectiveness of epidemic prevention and control and its impact on the quality of nosocomial infection management. METHODS The infection control measures of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were summarized and refined them into 16 quantitative assessment indicators, which will be inspected and assessed throughout the hospital from from Jul. to Dec. 2020. Data on epidemic prevention and control, incidence of nosocomial infection, hand hygiene related data during the same period were collected. RESULTS No confirmed cases of novel coronavirus pneumonia were found, and no asymptomatic infection cases were found to infect others. The incidence of nosocomial infection from July to December 2020 decreased compared with the same period in 2019. Stratified analysis showed that the infection of upper respiratory tract, urinary tract and gastrointestinal tract were significantly reduced, while there was no significant change in the infection rate of the type I incision surgical sites, the incidence of intravascular catheter related bloodstream infection, the incidence of ventilator-associated pneumonia and the incidence of catheter-related urinary tract infection. The compliance of hand hygiene, the accuracy of hand hygiene and the standard rate of hand disinfectant consumption were significantly improved, while there was no significant change in the consumption of dry hand tissue and hand sanitizer. CONCLUSION Quantitative assessment can effectively evaluate the implementation of normalized prevention and control measures of epidemic situation. The timely detection and elimination of potential epidemic hazards will have a positive impact on the improvement of the quality of nosocomial infection management.

4.
Signal Transduct Target Ther ; 6(1): 343, 2021 09 16.
Article in English | MEDLINE | ID: covidwho-1415924

ABSTRACT

SARS-CoV-2 recognizes, via its spike receptor-binding domain (S-RBD), human angiotensin-converting enzyme 2 (ACE2) to initiate infection. Ecto-domain protein of ACE2 can therefore function as a decoy. Here we show that mutations of S19W, T27W, and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding. Y330 could be synergistically combined with either W19 or W27, whereas W19 and W27 are mutually unbeneficial. The structures of SARS-CoV-2 S-RBD bound to the ACE2 mutants reveal that the enhanced binding is mainly contributed by the van der Waals interactions mediated by the aromatic side-chains from W19, W27, and Y330. While Y330 and W19/W27 are distantly located and devoid of any steric interference, W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts, explaining their incompatibility. Finally, using pseudotyped SARS-CoV-2 viruses, we demonstrate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses. Taken together, our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W, T27W, and N330Y mutations in ACE2, paving the way for potential application of these mutants in clinical treatment of COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/chemistry , COVID-19 , Molecular Dynamics Simulation , Mutation, Missense , SARS-CoV-2/chemistry , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Viral/chemistry , Antibodies, Viral/metabolism , Humans , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
6.
MedComm (2020) ; 2021 May 17.
Article in English | MEDLINE | ID: covidwho-1222647

ABSTRACT

The emerging variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in pandemic call for the urgent development of universal corona virus disease 2019 (COVID-19) vaccines which could be effective for both wild-type SARS-CoV-2 and mutant strains. In the current study, we formulated protein subunit vaccines with AS03 adjuvant and recombinant proteins of S1 subunit of SARS-CoV-2 (S1-WT) and S1 variant (K417N, E484K, N501Y, and D614G) subunit (S1-Mut), and immunized transgenic mice that express human angiotensin-converting enzyme 2 (hACE2). The S1 protein-specific antibody production and the neutralization capability for SARS-CoV-2 and B.1.351 variant were measured after immunization in mice. The results revealed that the S1-Mut antigens were more effective in inhibiting the receptor-binding domain and ACE2 binding in B.1.351 variant than in wild-type SARS-CoV-2. Furthermore, the development of a bivalent vaccine exhibited the ideal neutralization properties against wild-type and B.1.351 variant, as well as other variants. Our findings may provide a rationale for the development of a bivalent recombinant vaccine targeting the S1 protein that can induce the neutralizing antibodies against both SARS-CoV-2 variants and wild-type of the virus and may be of importance to explore the potential clinical use of bivalent recombinant vaccine in the future.

9.
Nature ; 586(7830): 572-577, 2020 10.
Article in English | MEDLINE | ID: covidwho-691301

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing/immunology , COVID-19 , COVID-19 Vaccines , Humans , Macaca mulatta/immunology , Macaca mulatta/virology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Models, Animal , Models, Molecular , Protein Domains , SARS-CoV-2 , Serum/immunology , Spleen/cytology , Spleen/immunology , T-Lymphocytes/immunology , Vaccination
10.
Int J Infect Dis ; 99: 3-7, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-676775

ABSTRACT

BACKGROUND: Few studies have explored air and surface contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare settings. METHODS: Air and surface samples were collected from the isolation wards and intensive care units designated for coronavirus disease 2019 (COVID-19) patients. Clinical data and the results of nasopharyngeal specimen and serum antibody testing were also collected for the patient sample. RESULTS: A total of 367 air and surface swab samples were collected from the patient care areas of 15 patients with mild COVID-19 and nine patients with severe/critical COVID-19. Only one air sample taken during the intubation procedure tested positive. High-touch surfaces were slightly more likely to be contaminated with SARS-CoV-2 RNA than low-touch surfaces. Contamination rates were slightly higher near severe/critical patients than near mild patients, although this difference was not statistically significant (p > 0.05). Surface contamination was still found near the patients with both positive IgG and IgM. CONCLUSIONS: Air and surface contamination with viral RNA was relatively low in these healthcare settings after the enhancement of infection prevention and control. Environmental contamination could still be found near seroconverted patients, suggesting the need to maintain constant vigilance in healthcare settings to reduce healthcare-associated infection during the COVID-19 pandemic.


Subject(s)
Air Microbiology , Betacoronavirus , Coronavirus Infections/virology , Fomites , Pneumonia, Viral/virology , Tertiary Care Centers , COVID-19 , China , Humans , Intensive Care Units , Pandemics , SARS-CoV-2
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