Rapid development of an inactivated vaccine for SARS-CoV-2

Gao, Qiang; Bao, Linlin; Mao, Haiyan; Wang, Lin; Xu, Kangwei; Yang, Mu; Li, Yajing; Zhu, Ling; Wang, Nan; Lv, Zhe; Gao, Hong; Cai, Fang; Kan, Biao; Hu, Yaling; Liu, Jiangning; Jiang, Deyu; Qin, Cheng‐Feng; Li, Jing; Gong, Xuejie; Fang, Zhiguo; Shi, Wen; Wu, Dongdong; Zhang, Hengming; Zhu, Lang; Deng, Wei; Li, Yurong; Lu, Jinxing; Li, Changgui; Wang, Xiangxi; Yin, Weidong; Zhang, Yanjun; Qin, Chuan

doi:10.1101/2020.04.17.046375

Cited by 94 publications

(104 citation statements)

References 20 publications

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“…First, EM images of a β-propiolactone inactivated SARS-CoV-2 virus preparation, purified by a potassium tartrate-glycerol density gradient, appeared to have lost all S1 subunits, leaving only the postfusion S2 on the virion surfaces 38 . Likewise, EM images of a β-propiolactone inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) also showed needle-like spikes on its surfaces 39 . Second, there are elongated spikes on the surfaces of live viruses in the images released to the news media (http://nmdc.cn/#/nCoV).…”

Section: Architecture Of S Protein On the Surface Of Sars-cov-2 Virionmentioning

confidence: 98%

Distinct conformational states of SARS-CoV-2 spike protein

Cai

Zhang

Xiao

et al. 2020

Preprint

289

539

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The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes -the first key step of viral infection. Here we report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1Å resolution) and postfusion (3.3Å resolution) conformations, respectively.The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance our understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.

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Section: Architecture Of S Protein On the Surface Of Sars-cov-2 Virionmentioning

confidence: 98%

Distinct conformational states of SARS-CoV-2 spike protein

Cai

Zhang

Xiao

et al. 2020

Preprint

289

539

View full text Add to dashboard Cite

show abstract

“…candidates expressing viral proteins and immunomodulatory genes (Shenzhen Geno-Immune Medical Institute; Trial IDs: NCT04299724 and NCT04276896). [70][71][72][73][74][75] Launching clinical trials within four months from SARS-CoV-2 discovery represents an incredible achievement for vaccine developers, with the mRNA vaccine being injected into an adult volunteer only 65 days after genomic elucidation. 70 This feat was made possible by advances in vaccine technology including the development of mRNA and vectored-based platforms that were tested in other emerging virus vaccines.…”

Section: For Example Virus-specific Cd8+ T Cells Play An Important Rmentioning

confidence: 99%

Lessons From COVID-19 in Children: Key Hypotheses to Guide Preventative and Therapeutic Strategies

Singh

Heston

Langel

et al. 2020

Clinical Infectious Diseases

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The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), reveals a peculiar trend of milder disease and lower case fatality in children compared with adults. Consistent epidemiologic evidence of reduced severity of infection in children across different populations and countries suggests there are underlying biological differences between children and adults that mediate differential disease pathogenesis. This presents a unique opportunity to learn about disease-modifying host factors from pediatric populations. Our review summarizes the current knowledge of pediatric clinical disease, role in transmission, risks for severe disease, protective immunity, as well as novel therapies and vaccine trials for children. We then define key hypotheses and areas for future research that can use the pediatric model of disease, transmission, and immunity to develop preventive and therapeutic strategies for people of all age groups.

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“…The global outbreak of COVID-19 has emerged as a severe threat to human health (1)(2)(3)(4) , claiming over two hundred and sixty thousand lives as 7 May, 2020 (5). COVID-19 is caused by a novel coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped, positive-strand RNA virus that causes upper respiratory diseases, fever and 40 severe pneumonia in humans (2, 3,6).…”

mentioning

confidence: 99%

A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

Chi

Yan

Zhang

et al. 2020

Preprint

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The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory 20 syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-25 terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 30 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.35was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

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Rapid development of an inactivated vaccine for SARS-CoV-2

Cited by 94 publications

References 20 publications

Distinct conformational states of SARS-CoV-2 spike protein

Distinct conformational states of SARS-CoV-2 spike protein

Lessons From COVID-19 in Children: Key Hypotheses to Guide Preventative and Therapeutic Strategies

A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

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