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Development of Improved Mumps Vaccine Candidates by Mutating Viral mRNA Cap Methyltransferase Sites in the Large Polymerase Protein
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作者 Xiaoqiang Hao Yilong Wang +5 位作者 Mengying Zhu Dongming Zhou Rongxian Liu Bin Wang Yao-Wei Huang Zhengyan Zhao 《Virologica Sinica》 SCIE CAS CSCD 2021年第3期521-536,共16页
Although a live attenuated vaccine is available for controlling mumps virus(MuV), mumps still outbreaks frequently worldwide. The attenuated MuV vaccine strain S79 is widely used in mumps vaccination in China, but sti... Although a live attenuated vaccine is available for controlling mumps virus(MuV), mumps still outbreaks frequently worldwide. The attenuated MuV vaccine strain S79 is widely used in mumps vaccination in China, but still with many shortcomings, among which the most prominent are the side effects and decreased immunity. Therefore, there is a need to further improve the safety and efficacy of the current MuV vaccine. In the present study, we further attenuated MuV S79 vaccine strain by inhibiting viral mRNA methyltransferase(MTase). We generated a panel of eight recombinant MuVs(rMuVs) carrying mutations in the MTase catalytic site or S-adenosylmethionine(SAM) binding site in the large(L) polymerase protein. These rMuVs are genetically stable and seven rMuVs are more attenuated in replication in cell culture and five r MuVs are more attenuated in replication in lungs of cotton rats compared with the parental vaccine strain S79. Importantly, cotton rats vaccinated with these seven rMuV mutants produced high levels of serum neutralizing antibodies and were completely protected against challenge with a wild-type MuV strain(genotype F). Therefore, our results demonstrate that alteration in the MTase catalytic site or SAM binding site in MuV L protein improves the safety or the immunogenicity of the MuV vaccine and thus mRNA cap MTase may be an effective target for the development of new vaccine candidates for MuV. 展开更多
关键词 Mumps virus(MuV) VACCINE Methyltransferase(MTase) Large polymerase protein
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Future of the current anticoronaviral agents: A viewpoint on thevalidation for the next COVIDs and pandemics
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作者 AMGAD M.RABIE 《BIOCELL》 SCIE 2023年第10期2133-2139,共7页
Despite the global decline in the severity of the coronavirus disease 2019 (COVID-19) cases, the disease stillrepresents a major concern to the relevant scientific and medical communities. The primary concern of drug ... Despite the global decline in the severity of the coronavirus disease 2019 (COVID-19) cases, the disease stillrepresents a major concern to the relevant scientific and medical communities. The primary concern of drug scientists,virologists, and other concerned specialists in this respect is to find ready-to-use suitable and potent anticoronaviraltherapies that are broadly effective against the different species/strains of the coronaviruses in general, not only againstthe current and previous coronaviruses (e.g., the recently-appeared severe acute respiratory syndrome coronavirus 2“SARS-CoV-2”), i.e., effective antiviral agents for treatment and/or prophylaxis of any coronaviral infections, includingthose of the coming ones from the next species and strains (if any). As an expert in this field, I tried, in this up-to-dateperspective “viewpoint” article, to evaluate the suitability and applicability of using the currently-availableanticoronaviral agents for the next coronavirus diseases (COVIDs) and coronaviral pandemics, highlighting the mostimportant general guidelines that should be considered in the next pandemics from the therapeutic points of view. 展开更多
关键词 SARS-CoV-2/COVID-19 Spike(S)protein/Main protease(Mpro)/RNA-dependent RNA polymerase(RdRp) General anticoronaviral drug Specific anti-COVID-19 medication Molnupiravir/Nirmatrelvir/Riboprine/Ensitrelvir Drug design and development
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Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics 被引量:6
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作者 钱小顺 朱元珏 +1 位作者 许文兵 林耀广 《Chinese Medical Journal》 SCIE CAS CSCD 2001年第10期43-46,106,共5页
Objective To investigate the expression of glucocerticoid receptor (GR) and heat shock protein 90(HSP90) mRNA in peripheral blood mononuclear cells (PBMCs) from steroid-sensitive (SS), steroiddependent (SD) and stero... Objective To investigate the expression of glucocerticoid receptor (GR) and heat shock protein 90(HSP90) mRNA in peripheral blood mononuclear cells (PBMCs) from steroid-sensitive (SS), steroiddependent (SD) and steroid-resistant (SR) asthmatics patients, and to evaluate the role of GR and HSP90in the pathogenesis of SR.Methods Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expressions of GR and HSP90 mRNA in PBMC stimulated with IL-2 and/or IL-4 from 10 normal volunteers,10 SS, 5 SD and 6 SR patients.Results The expressions of GR and HSP90 mRNA were the highest in PBMC from SR patients (0.730±0.171 and 1.122±0.165, respectively) compared with the normals (P<0.05). The second was from SS patients (0.359±0.350 and 0.885±0.250, respectively). The lowest was from the SD patients (0.017±0.008 and 0.078 ± 0.039, respectively). The ratio of HSP90/GR in SR was significantly lower than that in the others, and it suggested that the expression of HSP90 mRNA was not sufficient in this group of patients. When PBMC from SS, SD and SR was incubated with IL-2 or IL-4 alone, no changes in GR and HSP90 mRNA expression were observed. While incubated with combination of IL-2 and IL-4, a significantly higher expression of GR mRNA was observed in all asthmatics, and a significantly higher expression of HSP90 mRNA was observed only in SS and SD patients.Conclusion The lowering of HSP90/GR ratio may be one of the causes of SR. IL-2 and IL-4 may play roles in the imbalance of HSP90/GR. 展开更多
关键词 asthma · glucocorticoid receptor · heat shock protein 90 · reverse transcription polymerase chain reaction · peripheral blood mononuclear cell
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Naturally occurring PA^(E206K)point mutation in 2009 H1N1 pandemic influenza viruses impairs viral replication at high temperatures
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作者 Mengmeng Cao Qiannan Jia +5 位作者 Jinghua Li Lili Zhao Li zhu Yufan Zhang Shan Li Tao Deng 《Virologica Sinica》 SCIE CAS CSCD 2024年第1期71-80,共10页
The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century.In this study,we observed significant differences in the polymerase activities of two clinical 2009 H1N1 inf... The emergence of influenza virus A pandemic H1N1 in April 2009 marked the first pandemic of the 21st century.In this study,we observed significant differences in the polymerase activities of two clinical 2009 H1N1 influenza A virus isolates from Chinese and Japanese patients.Sequence comparison of the three main protein subunits(PB2,PB1,and PA)of the viral RNA-dependent RNA polymerase complex and subsequent mutational analysis revealed that a single amino acid substitution(E206K)was responsible for the observed impaired replication phenotype.Further in vitro experiments showed that presence of PAE206K decreased the replication of influenza A/WSN/33 virus in mammalian cells and a reduction in the virus’s pathogenicity in vivo.Mechanistic studies revealed that PAE206K is a temperature-sensitive mutant associated with the inability to transport PB1–PA complex to the nucleus at high temperature(39.5℃).Hence,this naturally occurring variant in the PA protein represents an ideal candidate mutation for the development of live attenuated influenza vaccines. 展开更多
关键词 H1N1 Influenza A virus polymerase acidic protein Point mutation Viral replication
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