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1.
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
2.
EBioMedicine ; 76: 103841, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1649699

ABSTRACT

Currently licensed COVID-19 vaccines are all designed for intramuscular (IM) immunization. However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation. Despite the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the next generation of COVID-19 vaccine is in demand and intranasal (IN) vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses. Presently, although not licensed, various IN vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases. In this review, we give a detailed description about current status of IN COVID-19 vaccines, including virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines. The ongoing clinical trials for IN vaccines are highlighted. Additionally, the underlying mechanisms of mucosal immunity and potential mucosal adjuvants and nasal delivery devices are also summarized.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Administration, Intranasal , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Clinical Trials as Topic , Humans , Immunity, Mucosal , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
3.
Bioact Mater ; 17: 29-48, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1624692

ABSTRACT

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

4.
Mol Biomed ; 2(1): 1, 2021.
Article in English | MEDLINE | ID: covidwho-1515457

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). COVID-19 can spread to the entire body and cause multiple organ failure. It is a daunting challenge to control the fast growing worldwide pandemic because effective prevention and treatment strategies are unavailable currently. Generally, the immune response of the human body triggered by viral infection is essential for the elimination of the virus. However, severe COVID-19 patients may manifest dysregulated immune responses, such as lymphopenia, lymphocyte exhaustion, exacerbated antibody response, cytokine release syndrome (CRS), etc. Understanding of these immunological characteristics may help identify better approaches for diagnosis, prognosis and treatment of COVID-19 patients. As specific anti-viral agents are notoriously difficult to develop, strategies for modulating the immune responses by either developing novel vaccines or using immunotherapy hold great promise to improve the management of SARS-CoV-2 infection.

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