Subjects: Biology >> Virology Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2021-07-28
Abstract: The origin of SARS-CoV-2 remains elusive. Understanding how, when, and where SARS-CoV-2 was transmitted from its natural reservoir to human beings is crucial for preventing future coronavirus outbreaks. With the lessons learned from the endless battle with pathogens and accumulated research data with regard to the origin and intermediate host, we present multiple potential locations as the natural reservoir of SARS-CoV-2.
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Subjects: Biology >> Virology Subjects: Medicine, Pharmacy >> Preventive Medicine and Hygienics submitted time 2021-07-17
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Subjects: Biology >> Virology submitted time 2020-04-19
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Subjects: Biology >> Virology submitted time 2020-03-06
Abstract: Global emergencies caused by the zoonotic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the newly discovered 2019 novel coronavirus (2019-nCoV) have posed a serious threat to human health. The spike (S) glycoprotein, a homotrimer located on the surface of the viral envelope, is the key antigen for therapeutic development. The S2 subunit from the S glycoprotein, which is highly conserved among coronaviruses, contributes to viral entry by mediating the host-viral membrane fusion. However, the structural information of the post-fusion S2 machinery from these highly pathogenic human-infecting coronaviruses is still lacking. Here, we report the structure of SARS-CoV S glycoprotein in the post-fusion state by single particle cryo-electron microscopy, revealing a more rotated HR1-HR2 six-helix bundle and a tightly bound linker region upstream of the HR2 motif that plays an important role in membrane fusion. Comparison with the structure of pre-fusion SARS-CoV S glycoprotein shows dramatic structural rearrangements and conformational changes, resembling that of the Mouse hepatitis virus (MHV) and other class I viral fusion proteins. By analyzing the structural features, describing the glycan shield and mapping the antibody and inhibitor targets on the surface of the post-fusion S glycoprotein, we provide structural basis of potential therapeutic targets within the highly conserved S2 subunit, which may help the development of effective vaccines and therapies against a wide range of SARS-like coronaviruses. " "
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Subjects: Biology >> Virology submitted time 2020-02-25
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。
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Subjects: Biology >> Virology submitted time 2020-02-22
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 Subjects: Biology >> Biological Evolution Subjects: Biology >> Genetics submitted time 2020-02-21
Abstract: Background. The outbreak of COVID-19 started in mid-December 2019 in Wuhan, Central China. Up to February 18, 2020, SARS-CoV-2 has infected more than 70,000 people in China, and another 25 countries across five continents. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to decode the evolution and human-to-human transmissions of SARS-CoV-2 in the recent two months. Methods. Alignment of coding-regions was conducted haplotype analyses using DnaSP. Substitution sites were analyzed in codon. Evolutionary analysis of haplotypes used NETWORK. Population size changes were estimated using both DnaSP and Arlequin. Expansion date of population size was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. Findings. Eight coding-regions have 120 substitution sites, including 79 non-synonymous and 40 synonymous substitutions. Forty-two non-synonymous substitutions changed the biochemical property of amino acids. No evident combination was found. Fifty-eight haplotypes were classified as five groups, and 31 haplotypes were found in samples from both China and other countries, respectively. The rooted network suggested H13 and H35 to be ancestral haplotypes, and H1 (and its descendent haplotypes including all samples from the Hua Nan market) was derived H3 haplotype. Population size of SARS-CoV-2 were estimated to have a recent expansion on 6 January 2020, and an early expansion on 8 December 2019. Interpretation. Genomic variations of SARS-CoV-2 are still low in comparisons with published genomes of SARS-CoV and MERS-CoV. Phyloepidemiologic analyses indicated the SARS-CoV-2 source at the Hua Nan market should be imported from other places. The crowded market boosted SARS-CoV-2 rapid circulations in the market and spread it to the whole city in early December 2019. Furthermore, phyloepidemiologic approaches have recovered specific direction of human-to-human transmissions, and the import sources of international infectious cases.
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
Subjects: Biology >> Virology submitted time 2019-01-29
Abstract: In this study, we aimed to detect viruses in hard ticks using the small RNA sequencing based method. A 235-bp DNA segment was detected in Dermacentor nuttalli (hard ticks) and D. silvarum (hard ticks) from sheep and bovine, respectively. The detected 235-bp segment had an identity of 99% to a 235-bp DNA segment of African Swine Fever Virus (ASFV) and contained three single nucleotide mutations (C38T, C76T and A108C). C38T, resulting in an single amino acid mutation G66D, suggests the existence of a new ASFV strain, which is different from all reported ASFV strains in NCBI GenBank database. These results also suggest that ASFV could have a wide range of hosts or vectors, beyond the well known Suidae family and soft ticks. Our findings pave the way toward further studies of ASFV transmission and development of prevention and control measures." " "
Peer Review Status:Awaiting Review
Subjects: Biology >> Biomedical Laboratory Science Subjects: Biology >> Virology submitted time 2017-07-11
Abstract:Objective: Viral clearance of human HBV infection largely depends on the age of exposure, so a mouse model with age-dependent immune response and immune-tolerance for HBV infection is essential. Methods: HBVRag1 mice were generated by crossing Rag1-/- mice with HBV-Tg mice. The differences between adult and young HBVRag1 mice were detected after adoptive transfer of splenocytes. Immune tolerance was evaluated by quantitative hepatitis B core antibody (qAnti-HBc) assay, adoptive transfer, and modulation of gut microbiota with antibiotic. Results: After HBVRag1 mouse reconstitution, adult mice showed obvious HBV-dependent inflammation and hepatocytes damage, cleared HBsAg and generated HBsAb and HBcAb, but young mice never developed ALT elevation, and only generated HBcAb with persistence of HBsAg. In addition, for adult mice, more hepatic CD8+T and B cells promoted clearance of HBsAg 30 days after lymphocytes transfer, and for young mice, higher levels of cytokines link to the persistence of viral antigens during initiation of immune response towards HBV. The level of qAnti-HBc increased significantly with the time of adoptive transfer in young mice, but decreased significantly in adult within our model. This mimics kinetic changes of human HBV infection regarding qAnti-HBc level. Also, the age-related tolerance in this model was different from which was in HBV-Tg mice, and can be regulated through modulation of gut microbiota. Meanwhile, GS-9620 can achieve inhibition of HBsAg, but HBV vaccine just clears limited HBsAg within the model. Conclusions: Here, we described a mouse model with age-dependent immune response and immune tolerance of HBV infection which could mimic chronic HBV infection in human. It will open a door for evaluating new therapeutic approaches before clinical trials.
Peer Review Status:Awaiting Review