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1.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-689222

ABSTRACT

BackgroundThe outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease

2.
EClinicalMedicine ; 2020.
Article | WHO COVID | ID: covidwho-684336

ABSTRACT

Background The outbreak of a new coronavirus (SARS-CoV-2) poses a great challenge to global public health New and effective intervention strategies are urgently needed to combat the disease Methods We conducted an open-label, non-randomized, clinical trial involving moderate COVID-19 patients according to study protocol Patients were assigned in a 1:2 ratio to receive either aerosol inhalation treatment with IFN-κ and TFF2, every 48 h for three consecutive dosages, in addition to standard treatment (experimental group), or standard treatment alone (control group) The end point was the time to discharge from the hospital This study is registered with chictr org cn, ChiCTR2000030262 Findings A total of thirty-three eligible COVID-19 patients were enrolled from February 1, 2020 to April 6, 2020, eleven were assigned to the IFN-κ plus TFF2 group, and twenty-two to the control group Safety and efficacy were evaluated for both groups No treatment-associated severe adverse effects (SAE) were observed in the group treated with aerosol inhalation of IFN-κ plus TFF2, and no significant differences in the safety evaluations were observed between experimental and control groups CT imaging was performed in all patients with the median improvement time of 5 0 days (IQR 3 0–9 0) in the experimental group versus 8 5 days (IQR 3 0–17 0) in the control group (p<0 05) In addition, the experimental group had a significant shorten median time in cough relief (4 5 days [IQR 2 0–7 0]) than the control group did (10 0 days [IQR 6 0–21 0])(p<0 005), in viral RNA reversion of 6 0 days (IQR 2 0–13 0) in the experimental group vs 9 5 days (IQR 3 0–23 0) in the control group (p < 0 05), and in the median hospitalization stays of 12 0 days (IQR 7 0–20 0) in the experimental group vs 15 0 days (IQR 10 0–25 0) in the control group (p<0 001), respectively Interpretation Aerosol inhalation of IFN-κ plus TFF2 is a safe treatment and is likely to significantly facilitate clinical improvement, including cough relief, CT imaging improvement, and viral RNA reversion, thereby achieves an early release from hospitalization These data support to explore a scale-up trial with IFN-κ plus TFF2 Funding National Major Project for Control and Prevention of Infectious Disease in China, Shanghai Science and Technology Commission, Shanghai Municipal Health Commission

3.
Cell Rep ; 32(3): 107918, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-625076

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC50 below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC50 within 10 nM, and the best one, 414-1, with IC50 of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Receptors, Virus/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , Coronavirus Infections/therapy , Epitope Mapping , Epitopes/immunology , Humans , Immunologic Memory/immunology , Neutralization Tests , Pandemics , Pneumonia, Viral/therapy , Protein Domains/immunology
4.
Cell Mol Immunol ; 17(6): 621-630, 2020 06.
Article in English | MEDLINE | ID: covidwho-262594

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Betacoronavirus/immunology , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Amino Acid Motifs , Animals , Antibodies, Monoclonal/immunology , Antibodies, Viral/metabolism , Betacoronavirus/metabolism , Betacoronavirus/physiology , Binding Sites , Cross Reactions , Epitopes , HEK293 Cells , Humans , Male , Mice , Mice, Inbred C57BL , Protein Interaction Domains and Motifs/immunology , Receptors, Virus/metabolism , SARS Virus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Virus Internalization
6.
Journal of Bio-X Research ; Latest Articles, 2020.
Article | WHO COVID | ID: covidwho-10224
8.
Ann. Transl. Med. ; 3(8)20200201.
Article in English | ELSEVIER | ID: covidwho-4170

ABSTRACT

Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.

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