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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.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323684

ABSTRACT

Background: Studies are needed to provide evidence for the immunization strategy of the COVID-19 vaccine simultaneously administered with the influenza vaccine. Methods: A randomised, open-label, controlled, phase 4 clinical trial was conducted in Zhejiang Province, east of China. Eligible healthy adults aged 18–59 years underwent randomization at a ratio of 1:1:2 to receive one dose of inactivated quadrivalent influenza vaccine (IIV4) either simultaneously with the first (SI1 subgroup, Day 0) or the second (SI2 subgroup, Day 28) dose of CoronaVac, or 14 days after the first dose of CoronaVac (SE group). The primary endpoint of the study was the non-inferiority in seroconversion rate of antibody against SARS-Cov-2 between participants who received two vaccines simultaneously and those who followed the separate vaccination schedule (clinicaltrials.gov number, NCT04801888). Findings: Overall, 480 participants were enrolled, with 120, 120, and 240 randomly assigned to the SI1, SI2, and SE groups, respectively. With the noninferiority margin set at 10%, the seroconversion of antibodies against SARS-CoV-2 in the SI group (93.11% [89.04, 96.01]) was not inferior to that in the SE group (95.15% [91.50, 97.56]) in the per-protocol set. Overall, the geometric mean titer (GMT) in the SE group was higher than that in the SI group with statistical significance (38.06 vs. 27.54, P=0.0001). Within the SI group, the GMT was significantly higher in the SI1 subgroup than that in the SI2 subgroup (32.61 vs 23.26, P=0.0153). The occurrences of vaccine related adverse reactions were comparable among different vaccination groups (16.67% vs. 19.17% and 20.00%, P=0.7568).Interpretation: Simultaneous administration of both SARS-Cov-2 inactivated vaccine and seasonal influenza vaccine would be feasible. Further studies are needed to explain the unexpected decrease of immune response against SARS-CoV-2 following the regimen that IIV4 simultaneously administered with the 2 nd dose of the SARS-CoV-2 inactivated vaccine.Trial Registration: This study was registered at: (clinicaltrials.gov number, NCT04801888).Funding: This study was funded by the Vaccine Clinical Evaluation Platform Construction Project under China National Science and Technology Major Projects [2018ZX09734004] and The Key Research and Development Program of Zhejiang Province (2021C03200).Declaration of Interest: GZ, XD and ZW are employees of Sinovac Biotech CO., Ltd. All other authors declare no competing interests.Ethical Approval: The study protocol and informed consent form were approved by the ethics committee of the Zhejiang Provincial Center for Disease Control and Prevention (ZJCDC).

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315882

ABSTRACT

Background: The outbreak and pandemic of coronavirus SARS CoV 2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single‑chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS CoV 2 spike interaction with ACE2 protein were developed. Results: Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91 hFc and Nb3 hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91 Nb3 hFc exhibited the strongest RBD binding affinity and neutralizing ability against SARS CoV 2 pseudoviruses with an IC50 value at approximately 1.54 nM. Conclusions: The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91 Nb3 hFc may serve as a potential therapeutic agent for the treatment of COVID 19.

5.
J Nanobiotechnology ; 19(1): 33, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1054825

ABSTRACT

BACKGROUND: The outbreak and pandemic of coronavirus SARS-CoV-2 caused significant threaten to global public health and economic consequences. It is extremely urgent that global people must take actions to develop safe and effective preventions and therapeutics. Nanobodies, which are derived from single­chain camelid antibodies, had shown antiviral properties in various challenge viruses. In this study, multivalent nanobodies with high affinity blocking SARS-CoV-2 spike interaction with ACE2 protein were developed. RESULTS: Totally, four specific nanobodies against spike protein and its RBD domain were screened from a naïve VHH library. Among them, Nb91-hFc and Nb3-hFc demonstrated antiviral activity by neutralizing spike pseudotyped viruses in vitro. Subsequently, multivalent nanobodies were constructed to improve the neutralizing capacity. As a result, heterodimer nanobody Nb91-Nb3-hFc exhibited the strongest RBD-binding affinity and neutralizing ability against SARS-CoV-2 pseudoviruses with an IC50 value at approximately 1.54 nM. CONCLUSIONS: The present study indicated that naïve VHH library could be used as a potential resource for rapid acquisition and exploitation of antiviral nanobodies. Heterodimer nanobody Nb91-Nb3-hFc may serve as a potential therapeutic agent for the treatment of COVID-19.


Subject(s)
Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Binding Sites , HEK293 Cells , Humans , Neutralization Tests , Protein Binding , Protein Domains , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors
6.
Braz J Cardiovasc Surg ; 36(4): 530-534, 2021 08 06.
Article in English | MEDLINE | ID: covidwho-1000762

ABSTRACT

INTRODUCTION: To investigate the effect of WeChat-based telehealth services on the postoperative follow-up of children who underwent congenital heart surgery during the COVID-19 epidemic. METHODS: This study retrospectively analyzed the clinical and family data of 108 children who underwent congenital heart surgery and underwent remote follow-up via the WeChat platform from December 2019 to March 2020 in our hospital. RESULTS: During the follow-up period, the WeChat platform was used to refer 8 children with respiratory infection symptoms to local hospitals for treatment. Two children with poor incision healing were healed after we used the WeChat platform to guide the parents in dressing the wounds on a regular basis at home. Nutritional guidance was given via the WeChat platform to 13 patients with poor growth and development. The psychological evaluation results of the parents showed that the median (range) SDS score was 43 (34-59), and 7 parents (6.5%) were classified as depressed; the median (range) SAS score was 41 (32-58), and 12 parents (11.1%) were classified as having mild anxiety. CONCLUSION: The use of WeChat-based telehealth services was effective for the remote postoperative follow-up of children who underwent congenital cardiac surgery during the COVID-19 epidemic. Providing WeChat-based telehealth services can reduce the amount of travel required for these children and their families, which is helpful for controlling and preventing the spread of COVID-19.


Subject(s)
COVID-19 , Cardiac Surgical Procedures , Epidemics , Child , Follow-Up Studies , Humans , Retrospective Studies , SARS-CoV-2
7.
Environ Technol Innov ; 19: 100987, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-597542

ABSTRACT

Concentrations of nine metals were measured in eight common cultured fish species obtained from forty-three aquatic product markets across three cities in Xinjiang province, to establish fingerprint characteristics and assess potential human health risks due to the consumption of fish. Metal levels ( µ g/kg, wet weight) in fish muscles were: 1204.88-5113.19 Al, 2.09-12.44 V, 6.10-31.86 Cr, 2368.80-8949.52 Fe, 2.01-10.26 Co, 4082.72-12785.68 Zn, 174.89-763.83 Cu, 0.33-2.24 Cd, and 5.74-9.90 Pb. Fingerprint analysis revealed that the studied fish species from the three cities exhibited a similar pattern of distribution. From the viewpoint of human health, the assessment of non-carcinogenic risk indicated no significant adverse health effects due to consumption of the assessed fish species.

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