Subjects: Biology >> Virology submitted time 2020-02-25
Xia, Jia
Lu, Guoliang
Lu, Jing
Zhang, Jiahui
Feng, Lin
Wang, Bing
Yu, Hang
Xu, Yingjie
Lin, Jinzhong
Abstract： Frequent outbreaks of coronavirus make the development of an effective vaccine imperative. Recently, vaccines based on in-vitro transcribed messenger RNA (mRNA) have shown great potential. The streamlined manufacturing of mRNA molecules, combined with the superior flexibility in the antigen screening, greatly accelerates the development process. When using an mRNA platform to develop a vaccine, initial antigen choice plays a crucial role in determining the final efficacy and safety of the vaccine. Furthermore, mRNA sequences that encode antigens require extensive optimization to ensure highly efficient and sustained expression. Our ongoing efforts to develop an effective mRNA vaccine against 2019-nCoV place emphasis on the virus-like particles (VLPs) as the presenting antigen. At the same time, our second fast track uses mRNA to express the receptor-binding domain of the spike protein(S-RBD). After extensive optimization, an mRNA cocktail containing three genes is able to produce 2019-nCoV virus-like particles highly similar to the native 2019-nCoV. Meanwhile, an mRNA vaccine candidate expressing S-RBD is being tested in mice for its immunogenicity. We will next compare both the efficacy and the safety of the two mRNA vaccines based on S-RBD and VLPs, respectively.
Peer Review Status:
Awaiting Review
Subjects: Physics >> Interdisciplinary Physics and Related Areas of Science and Technology Subjects: Biology >> Virology submitted time 2020-02-25
Abstract： 由于春运出湖北省高峰和全国各地管控开始之间的时间差，使得在这个时间段内，除湖北外的国内地区是个输入一代到感染二代之间独立自然连续传播体系。基于此，我们使用正态分布的线性叠加来拟合全国除湖北外每日新增的数据，简单模型预测和实际新增结果的高度吻合验证了除湖北外是个近似理想系统。拟合计算得到的新冠病毒可再生系数R0=2.2，一代到二代的峰值传播时间是7天。我们还讨论了偏离理想传播体系的原因并分析了一些省的特殊情况。
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology submitted time 2020-02-22
Mu, Jingfang
Xu, Jiuyue
Shu, Ting
Wu, Di
Huang, Muhan
Ren, Yujie
Li, Xufang
Geng, Qing
Xu, Yi
Qiu, Yang
Zhou, Xi
Abstract： The SARS-CoV-2 outbreak has emerged and is still ongoing in Wuhan and other areas of China and world. Human infections by SARS-CoV-2 lead to diseases ranging from mild symptoms to severe pneumonia and even death. And in the current situation, better understanding of the virology and virus-host interactions of SARS-CoV-2 would be vital for the efforts to control the infections and develop effective therapies. RNA interference (RNAi) is an evolutionarily conserved antiviral immune mechanism in diverse eukaryotic organisms, and numerous viruses have been found to encode their own viral suppressors of RNAi (VSRs) as countermeasures. In this study, we uncovered that the nucleocapsid (N) protein encoded by SARS-CoV-2 effectively suppressed RNAi triggered by either small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) in cultured human cells. Furthermore, similar with VSRs encoded by other viruses, SARS-CoV-2 N protein shows double-stranded RNA (dsRNA)-binding activity, as it interacted with in vitro transcribed dsRNAs in human cells. Taken together, our findings showed that SARS-CoV-2 N exhibits the VSR activity in human cells, which could be as a key immune evasion factor for SARS-CoV-2 and contribute to its pathogenicity. "
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology Subjects: Computer Science >> Other Disciplines of Computer Science submitted time 2020-02-21
Abstract： During the outbreak of new infectious diseases, there is an urgent need to put forward scientific hypotheses for the efficacy, mechanism and side effects of candidate drugs. The research and development of vaccines or new drugs need a certain period of time, so the strategy of drug repositioning has its place. However, the clinical data of pathogen and host response of new diseases are not ready, restricts the hypothesis of candidate drugs. At this stage, we often try to use broad-spectrum antiviral drugs according to the clinical characteristics of patients. In this paper, we propose a new method aCODE (agile discovery method of drugs or natural products for emerging epidemic) which based on the heuristic search strategy widely used in the field of artificial intelligence. Based on the broad-spectrum antiviral drugs with some early efficacy tips, the host target protein collection is obtained, and the associated gene modules is searched on the whole genome scale. We then carry out pattern matching and statistics for candidate compounds (such as approved drugs and natural products ingredients). This method can update the input drugs according to the progress of clinical practice, and output more accurate results iteratively. The output components from natural products, traditional Chinese medicine or food can be used for quick trial to form a closed loop of agile R & D test. In addition, for the second update of this method and its comparison with literature evidence, please refer to: http://chinaxiv.org/abs/202002.00024.
Peer Review Status:Awaiting Review
Subjects: Biology >> Virology submitted time 2020-02-14
Abstract： Abstract: In 2019, the 2019 novel Coronavirus (2019-nCoV) has caused the pneumonia outbreak in Wuhan (a city of China). In our previous study, the analytical results showed that both 2019-nCoV and SARS coronavirus belongs to Betacoronavirus subgroup B (BB coronavirus), but have large differences. The most important finding was that the alternative translation of Nankai CDS could produce more than 17 putative proteins, which may be responsible for the host adaption. The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of betacoronavirus. The present study for the first time reported a very important mutation in the Spike (S) proteins of BB coronavirus. By this mutation, 2019-nCoV acquired a cleavage site for furin enzyme, which is not present in the S proteins of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). This mutation may increase the efficiency of virus infection into cells, making 2019-nCoV has significantly stronger transmissibility than SARS coronavirus. Because of this mutation, the packing mechanism of the 2019-nCoV may be changed to being more similar to those of MHV, HIV, Ebola virus (EBoV) and some avian influenza viruses, other than those of all other BB coronavirus (e.g. SARS coronavirus) except the Mouse Hepatitis coronavirus (MHV). In addition, we unexpectedly found that some avian influenza viruses acquired a cleavage site for furin enzyme by mutation as 2019-nCoV. Further studies of this mutation will help to reveal the stronger transmissibility of 2019-nCoV and lay foundations for vaccine development and drug design of, but not limited to 2019-nCoV.
Peer Review Status:Awaiting Review
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