Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,...Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.展开更多
The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium ...The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis(Mtb)through various pattern recognition receptors(PRRs),including but not limited to Toll-like receptors(TLRs),Nod-like receptors(NLRs)and C-type lectin receptors(CLRs).Upon infection by Mtb,the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis,autophagy,apoptosis and inflammasome activation.In contrast,Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity.Here we discuss recent research on major host innate immune cells,PRR signaling,and the cellular functions involved in Mtb infection,with a specific focus on the host’s innate immune defense and Mtb immune evasion.A better understanding of the molecular mechanisms underlying host–pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.展开更多
Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of internatio...Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.展开更多
The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to ch...The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.展开更多
According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiol...According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.展开更多
Background:The diagnosis of active pulmonary tuberculosis(TB)remains a challenge in clinic,especially for sputum negative pulmonary TB.Bronchoalveolar lavage fluid(BALF)has higher sensitivity than sputum for detection...Background:The diagnosis of active pulmonary tuberculosis(TB)remains a challenge in clinic,especially for sputum negative pulmonary TB.Bronchoalveolar lavage fluid(BALF)has higher sensitivity than sputum for detection of Mycobacterium tuberculosis(Mtb).However,bronchoscopy is invasive and costly,and not suitable for all patients.In order to make TB patients get more benefit from BALF for diagnosis,we explore which indicator might be used to optimize the choice of bronchoscopy.Methods:A total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation.The sensitivity,specificity and accuracy of Mtb detection in sputum and BALF were compared.Odds ratios and 95%confidence intervals were used to assess variables that associated with positive acid-fast bacilli(AFB)smear,Mtb culture and nucleic acid amplification test(NAAT)of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects.Results:BALF has significantly higher sensitivity(63.4%)than sputum(43.5%)for Mtb detection by culture and NAAT.19.7%(122/620)sputum-negative and 40.0%(163/408)non-sputum-producing suspects had positive bacteriological results in BALF.Among sputum-negative and non-sputum-producing pulmonary TB suspects,the positivity of Mtb detection in BALF is associated with a younger age,the presence of pulmonary cavities and a positive result of interferon-gamma release assay(IGRA).Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8%positivity of Mtb in BALF.Conclusions:Our study indicated that combination of age,the presence of pulmonary cavity,and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects.Those who are under 35 years old,positive for the presence of pulmonary cavity and IGRA,should undergo bronchoscopy to collect BAFL for Mtb tests,as they have the highest possibility to get bacteriologically confirmation of TB.展开更多
Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the...Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the virus was traced back to a large seafood/wide animal market in Wuhan city.The serious clinical symptoms of the viral infection,including fever,dry cough,dys-pnea,and pneumonia,may result in progressive respiratory failure and even death.Moreover,the quick spread of the virus has caused an epidemic in China,as well as infection cases worldwide.The whole-genome sequence of Wuhan new virus(WH-Human_.1)was first released on January 10,2020(Zhang,2020),followed by additional ones released in Global Initiative on Sharing All Influ-enza Data(GISAID)(Shu and McCauley,2017).Later,this new virus was determined and announced as a new type of coronavirus(CoV;2019-nCoV)by the World Health Organization(WHO,2020a).展开更多
Geminiviruses are a group of plant viruses that cause severe diseases in many economically important crops worldwide, leading to devastating losses to agricultural production. Here we summarize the occurrence and dist...Geminiviruses are a group of plant viruses that cause severe diseases in many economically important crops worldwide, leading to devastating losses to agricultural production. Here we summarize the occurrence and distribution of geminiviruses in China,which provides valuable information for further epidemiological studies and supports the development of effective disease management strategies.展开更多
In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker arg...In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.展开更多
The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe ...The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)plays essential roles in virus replication and immune evasion,presenting a charming drug target.Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology,inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development.In this study,we sought to provide structural frameworks for PLpro inhibitor design.We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111 S,which shares many structural features of SARS-CoV PLpro.This crystal form has unique packing,high solvent content and reasonable resolution 2.5 A°,hence provides a good possibility for fragment-based screening using crystallographic approach.We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture.We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARSCoV-2 with the IC50 of 2.2?0.3 mmol/L.We then determined the structure of SARS-CoV-2 PLpro complexed by GRL0617 to 2.6 A°,showing the inhibitor accommodates the S3 e S4 pockets of the substrate binding cleft.The binding of GRL0617 induces closure of the BL2 loop and narrows the substrate binding cleft,whereas the binding of a tetrapeptide substrate enlarges the cleft.Hence,our results suggest a mechanism of GRL0617 inhibition,that GRL0617 not only occupies the substrate pockets,but also seals the entrance to the substrate binding cleft hence prevents the binding of the LXGG motif of the substrate.展开更多
Background Branch retinal vein occlusion （BRVO） is a common retinal vascular disorder of the elderly and both intravitreal triamcinolone acetonide （TA） and intravitreal bevacizumab were reported to be effective. T...Background Branch retinal vein occlusion （BRVO） is a common retinal vascular disorder of the elderly and both intravitreal triamcinolone acetonide （TA） and intravitreal bevacizumab were reported to be effective. The purpose of this study was to compare intravitreal bevacizumab with intravitreal TA for the treatment of macular edema resulting from BRVO. Methods The retrospectively comparative interventional study included a bevacizumab group of 34 BRVO patients （1.25 mg bevacizumab） and a TA group of 34 BRVO patients （4.0 mg TA）, and the two groups were matched by baseline best corrected visual acuity （BCVA）. Examinations were designed to be carried out at 1 day, 3 days, 1 month, 2 months, 3 months, 6 months and 1 year after each injection. The mean follow-up was （148.43±130.56） days. Main outcome parameters were BCVA and morphometric measurements of the macula obtained by optical coherence tomography. Results In all follow-ups, the mean changes of BCVA （LogMAR） between two groups were not significantly different （P 〉0.10）. Similarly, the rates of patients who got BCVA improvement ≥2 lines or lost BCVA ≥2 lines were not significantly different, either （P 〉0.10）. In both groups, compared with baseline, the mean central macular thickness （CMT） got reduction from 4 weeks to 1 year after initial injection, however, which lost statistical significance at 6-month follow-up in TA group （P=0.25） and lost significance at 3-month and 6-month follow-up in bevacizumab group （P=0.07, 0.21）. The mean CMT between two groups differed at 3-month follow-up （P 〈0.01）, while almost kept parallel in other follow-ups （all P 〉0.40）. In TA group, retinal pigment epithelium tear occurred in 1 eye at 8 weeks after initial injection and 12 eyes （35.3%） got intraocular pressure 〉21 mmHg. In bevacizumab group, no severe complications were observed. Conclusion For BRVO, intravitreal bevacizumab versus intravitreal TA causes a similar increase in visual acuity and reduct展开更多
Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all ar...Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all areas of China and even to other countries.The epidemic has caused 67,102 confirmed infections with 1526 fatal cases worldwide by February 14th,2020.展开更多
Dear Editor, First discovered during 1947 in Uganda from febrile rhesus macaques, Zika virus （ZIKV） is a mosquito-borne, reemerging flavivirus historically known to be present in much of Africa and Asia, occasionall...Dear Editor, First discovered during 1947 in Uganda from febrile rhesus macaques, Zika virus （ZIKV） is a mosquito-borne, reemerging flavivirus historically known to be present in much of Africa and Asia, occasionally causing outbreaks amongst the local populace （Haddow et al., 2012）. ZIKV infections in humans are mostly asymptomatic, but a small percentage of patients may show clinical symptoms such as a fever and rash, which resolve within a week or less.展开更多
SARS-CoV-2 is the pathogenic agent of COVID-19,which has evolved into a global pandemic.Compared with some other respiratory RNA viruses,SARS-CoV-2 is a poor inducer of type Ⅰ interferon(IFN).Here,we report that SARS...SARS-CoV-2 is the pathogenic agent of COVID-19,which has evolved into a global pandemic.Compared with some other respiratory RNA viruses,SARS-CoV-2 is a poor inducer of type Ⅰ interferon(IFN).Here,we report that SARS-CoV-2 nsp12,the viral RNA-dependent RNA polymerase(RdRp),suppresses host antiviral responses.SARS-CoV-2 nsp12 attenuated Sendai virus(SeV)-or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner.It also inhibited IFN promoter activation triggered by RIG-I,MDA5,MAVS,and IRF3 overexpression.Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3.Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12.Given these findings,our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.展开更多
In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute r...In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).展开更多
With the profound changes in the international security situation,the progression of globalization,and the continuous advancement of biotechnology,the risks and challenges posed by major infectious diseases and bioter...With the profound changes in the international security situation,the progression of globalization,and the continuous advancement of biotechnology,the risks and challenges posed by major infectious diseases and bioterrorism to the international community are also increasing.Biosafety,therefore,presents new opportunities for international cooperation and global governance.The world has become more integrated and now shares a common destiny in terms of biosafety.In the face of the current risks and challenges,the international community must work together to avert threats,advance mutual interests,and safeguard global biosecurity.In the context of the current situation regarding biosafety and biosecurity,we conducted the present analysis,and present here some appropriate countermeasures.展开更多
Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the ...Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the n展开更多
A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene con...A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.展开更多
The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guerin （BCG） booster vaccination in China was estimated using tuberculin skin testing （TST） and QuantiFERON-T...The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guerin （BCG） booster vaccination in China was estimated using tuberculin skin testing （TST） and QuantiFERON-TB Gold assay （QFT） to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5-15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST （induration ≥ 10 mm） and QFT positivity were 9.3% （264/2827） and 2.5% （71/2831）, respectively. The rate of QFT indeterminate result was 2.2% （62/2831）. The overall agreement between TST and QFT was low （concordance = 88.0%; K coefficient = 0.125）. Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26-2.31 ]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a two- step approach might be considered for TB infection testing among adolescents in China.展开更多
The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative m...The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative measures,pharmaceutical intervention is also crucial.Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS‐CoV‐2 and other coronaviruses.In this study,we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels,as well as molecular separation and characterization,to screen and identify natural products with antiviral activity.Using this workflow,we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods.We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS‐CoV‐2 infection and receptor binding domain‐human angiotensin‐converting enzyme 2(RBD‐hACE2)binding in vitro.Following charge‐and size‐based characterization of the active compounds through filtration and chromatographic fractionation,mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition.Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID‐19 and other diseases.展开更多
基金This study was supported by grants from the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2016-I2M-1-014)the National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(Nos.2017ZX10103004,2018ZX10305409,2017ZX10204401)the National Natural Science Foundation(No.81930063)
文摘Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
基金the National Key Research and Development Program of China(Grant Nos.2017YFA0505900 and 2017YFD0500300)the National Basic Research Programs of China(Grant No.2014CB74440)+2 种基金the National Natural Science Foundation of China(Grant Nos.81371769 and 81571954)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDPB03)the Youth Innovation Promotion Association CAS(Grant No.Y12A027BB2).
文摘The major innate immune cell types involved in tuberculosis(TB)infection are macrophages,dendritic cells(DCs),neutrophils and natural killer(NK)cells.These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis(Mtb)through various pattern recognition receptors(PRRs),including but not limited to Toll-like receptors(TLRs),Nod-like receptors(NLRs)and C-type lectin receptors(CLRs).Upon infection by Mtb,the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis,autophagy,apoptosis and inflammasome activation.In contrast,Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity.Here we discuss recent research on major host innate immune cells,PRR signaling,and the cellular functions involved in Mtb infection,with a specific focus on the host’s innate immune defense and Mtb immune evasion.A better understanding of the molecular mechanisms underlying host–pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.
基金This work was supported by the National Research and Development Project of China(Grant No.2020YFC0841100)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001)+3 种基金National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)National Mega projects of China for Major Infectious Diseases(Grant No.2017ZX10304402)and National Key Research and Development Programme of China(2016YFD0500301,2020YFC0840800,2020YFC0840900).
文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
基金This work was supported by the National Basic Research Program(973 Program)(No.2011CB504704)the Ministry of Health of China(2014ZX10004-001,2013ZX10004601).
文摘The newly emerged Middle East respiratory syndrome coronavirus(MERS-CoV)is a highly pathogenic respira-tory virus with pathogenic mechanisms that may be driven by innate immune pathways.The goal of this study is to characterize the expression of the structural(S,E,M,N)and accessory(ORF 3,ORF 4a,ORF 4b,ORF 5)proteins of MERS-CoV and to determine whether any of these pro-teins acts as an interferon antagonist.Individual structural and accessory protein-coding plasmids with an N-terminal HA tag were constructed and transiently transfected into cells,and their native expression and subcellular localiza-tion were assessed using Wes tern blotting and indirect immunofl uorescence.While ORF 4b demonstrated majorly nuclear localization,all of the other proteins demonstrated cytoplasmic localization.In addition,for the fi rst time,our experiments revealed that the M,ORF 4a,ORF 4b,and ORF 5 proteins are potent interferon antagonists.Further exami-nation revealed that the ORF 4a protein of MERS-CoV has the most potential to counteract the antiviral effects of IFN via the inhibition of both the interferon production(IFN-βpromoter activity,IRF-3/7 and NF-κB activation)and ISRE promoter element signaling pathways.Together,our re-sults provide new insights into the function and pathogenic role of the structural and accessory proteins of MERS-CoV.
基金supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the Chongqing Special Research Project for Novel Coronavirus Pneumonia Prevention and Control(No.cstc2020jscx-2 to L.Y.,No.cstc2020jscx-fyzx0074 to Y.C.,cstc2020jscx-fyzx0135 to Y.C.).
文摘According to the World Health Organization(WHO)newly updated situation report on March 18th,2020,the coronavirus disease 2019(COVID-19)pandemic has confirmed 191,127 cases and claimed 7807 deaths worldwide.1 The etiological agent of COVID-19 has been identified as a novel coronavirus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),belonging to Sarbecovirus subgenus(genus Betacoronavirus,family Coronaviridae)and showing 79.6 and 96.2%sequence identity in nucleotide to SARS-CoV and a bat coronavirus(BatCoV RaTG13),respectively.2–4 Like SARS-CoV infection,a substantial fraction of COVID-19 patients exhibits severe respiratory symptoms and has to be hospitalized in intensive care unit.5–8 Although the mortality rate of COVID-19 is significantly lower than that of SARS-CoV infection,SARS-CoV-2 shows much higher human-to-human transmission rate,rapidly leading to a global pandemic declared by WHO on March 11th,2020.
基金This study was supported by National Nature Science Foundation of China(81525016,81772145,81770013)Shenzhen Science&Technology Grant(JSGG20160427104724699,JCYJ20170412101048337,JCYJ20170412151620658)Sanming Project of Medicine in Shenzhen(GCZX2015043015340574).
文摘Background:The diagnosis of active pulmonary tuberculosis(TB)remains a challenge in clinic,especially for sputum negative pulmonary TB.Bronchoalveolar lavage fluid(BALF)has higher sensitivity than sputum for detection of Mycobacterium tuberculosis(Mtb).However,bronchoscopy is invasive and costly,and not suitable for all patients.In order to make TB patients get more benefit from BALF for diagnosis,we explore which indicator might be used to optimize the choice of bronchoscopy.Methods:A total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation.The sensitivity,specificity and accuracy of Mtb detection in sputum and BALF were compared.Odds ratios and 95%confidence intervals were used to assess variables that associated with positive acid-fast bacilli(AFB)smear,Mtb culture and nucleic acid amplification test(NAAT)of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects.Results:BALF has significantly higher sensitivity(63.4%)than sputum(43.5%)for Mtb detection by culture and NAAT.19.7%(122/620)sputum-negative and 40.0%(163/408)non-sputum-producing suspects had positive bacteriological results in BALF.Among sputum-negative and non-sputum-producing pulmonary TB suspects,the positivity of Mtb detection in BALF is associated with a younger age,the presence of pulmonary cavities and a positive result of interferon-gamma release assay(IGRA).Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8%positivity of Mtb in BALF.Conclusions:Our study indicated that combination of age,the presence of pulmonary cavity,and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects.Those who are under 35 years old,positive for the presence of pulmonary cavity and IGRA,should undergo bronchoscopy to collect BAFL for Mtb tests,as they have the highest possibility to get bacteriologically confirmation of TB.
基金We would like to thank Dr.Yongzhen Zhang from Shanghai Public Health Clinical Center,Fudan University,Shanghai,China,and Dr.Zhengli Shi from the Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,China,for providing the genome sequence of 2019-nCoV collected from Wuhan,China.This work is supported in part by grants from National Key R&D Program of China(2017YFC0908400,2017YFC1700200)National Natural Science Foundation of China(31900483).
文摘Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the virus was traced back to a large seafood/wide animal market in Wuhan city.The serious clinical symptoms of the viral infection,including fever,dry cough,dys-pnea,and pneumonia,may result in progressive respiratory failure and even death.Moreover,the quick spread of the virus has caused an epidemic in China,as well as infection cases worldwide.The whole-genome sequence of Wuhan new virus(WH-Human_.1)was first released on January 10,2020(Zhang,2020),followed by additional ones released in Global Initiative on Sharing All Influ-enza Data(GISAID)(Shu and McCauley,2017).Later,this new virus was determined and announced as a new type of coronavirus(CoV;2019-nCoV)by the World Health Organization(WHO,2020a).
基金supported by the National Natural Science Foundation of China (31720103914, 32172385)the National Key Research and Development Program of China (2021YFD1400400)the China National Tobacco Corporation (110202001030(JY-13))。
文摘Geminiviruses are a group of plant viruses that cause severe diseases in many economically important crops worldwide, leading to devastating losses to agricultural production. Here we summarize the occurrence and distribution of geminiviruses in China,which provides valuable information for further epidemiological studies and supports the development of effective disease management strategies.
文摘In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.
基金supported by the National Key Research and Development Program of China(2016YFD0500300)National Science and Technology Major Project(2018ZX10101001,China)+3 种基金National Natural Science Foundation of China(Grant Nos.81572005,81772207,81971985,11775308 and 81802057)Beijing Municipal Natural Science Foundation(Grant Nos.7182117 and 7174288,China)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant Nos.2017I2M-1-014 and 2016-I2M-1-013,China)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2018PT51009 and 2017PT31049,China)
文摘The pandemic of coronavirus disease 2019(COVID-19)is changing the world like never before.This crisis is unlikely contained in the absence of effective therapeutics or vaccine.The papain-like protease(PLpro)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)plays essential roles in virus replication and immune evasion,presenting a charming drug target.Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology,inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development.In this study,we sought to provide structural frameworks for PLpro inhibitor design.We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111 S,which shares many structural features of SARS-CoV PLpro.This crystal form has unique packing,high solvent content and reasonable resolution 2.5 A°,hence provides a good possibility for fragment-based screening using crystallographic approach.We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture.We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARSCoV-2 with the IC50 of 2.2?0.3 mmol/L.We then determined the structure of SARS-CoV-2 PLpro complexed by GRL0617 to 2.6 A°,showing the inhibitor accommodates the S3 e S4 pockets of the substrate binding cleft.The binding of GRL0617 induces closure of the BL2 loop and narrows the substrate binding cleft,whereas the binding of a tetrapeptide substrate enlarges the cleft.Hence,our results suggest a mechanism of GRL0617 inhibition,that GRL0617 not only occupies the substrate pockets,but also seals the entrance to the substrate binding cleft hence prevents the binding of the LXGG motif of the substrate.
基金This study was supported by a grant from the Beijing Natural Science Foundation （No. 7062065）.
文摘Background Branch retinal vein occlusion （BRVO） is a common retinal vascular disorder of the elderly and both intravitreal triamcinolone acetonide （TA） and intravitreal bevacizumab were reported to be effective. The purpose of this study was to compare intravitreal bevacizumab with intravitreal TA for the treatment of macular edema resulting from BRVO. Methods The retrospectively comparative interventional study included a bevacizumab group of 34 BRVO patients （1.25 mg bevacizumab） and a TA group of 34 BRVO patients （4.0 mg TA）, and the two groups were matched by baseline best corrected visual acuity （BCVA）. Examinations were designed to be carried out at 1 day, 3 days, 1 month, 2 months, 3 months, 6 months and 1 year after each injection. The mean follow-up was （148.43±130.56） days. Main outcome parameters were BCVA and morphometric measurements of the macula obtained by optical coherence tomography. Results In all follow-ups, the mean changes of BCVA （LogMAR） between two groups were not significantly different （P 〉0.10）. Similarly, the rates of patients who got BCVA improvement ≥2 lines or lost BCVA ≥2 lines were not significantly different, either （P 〉0.10）. In both groups, compared with baseline, the mean central macular thickness （CMT） got reduction from 4 weeks to 1 year after initial injection, however, which lost statistical significance at 6-month follow-up in TA group （P=0.25） and lost significance at 3-month and 6-month follow-up in bevacizumab group （P=0.07, 0.21）. The mean CMT between two groups differed at 3-month follow-up （P 〈0.01）, while almost kept parallel in other follow-ups （all P 〉0.40）. In TA group, retinal pigment epithelium tear occurred in 1 eye at 8 weeks after initial injection and 12 eyes （35.3%） got intraocular pressure 〉21 mmHg. In bevacizumab group, no severe complications were observed. Conclusion For BRVO, intravitreal bevacizumab versus intravitreal TA causes a similar increase in visual acuity and reduct
基金jointly funded by the National Key Research and Development Program of China (Grant No. 2017YFD0500104)National Natural Science Foundation of China (Grant Nos. 31470260, 81902070)+2 种基金the Science Fund for Distinguished Young Scholars of Hunan Province (Grant No. 2019JJ20004)the Provincial Natural Science Foundation of Hunan Province (Grant Nos. 2019JJ50035, 2020SK3001)the Fundamental Research Funds for the Central Universities of China (Grant No. 531107051162)。
文摘Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all areas of China and even to other countries.The epidemic has caused 67,102 confirmed infections with 1526 fatal cases worldwide by February 14th,2020.
文摘Dear Editor, First discovered during 1947 in Uganda from febrile rhesus macaques, Zika virus （ZIKV） is a mosquito-borne, reemerging flavivirus historically known to be present in much of Africa and Asia, occasionally causing outbreaks amongst the local populace （Haddow et al., 2012）. ZIKV infections in humans are mostly asymptomatic, but a small percentage of patients may show clinical symptoms such as a fever and rash, which resolve within a week or less.
基金supported by grants from the National Major Sciences&Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10733403 and 2018ZX10101001 to Z.X.,2018ZX10301401 to X.L. and Z.Z.)the National Natural Science Foundation of China(81930063,81971948,81772201,and 31670169 to J.W.,X.L.,Z.X.,and Z.Z.)+1 种基金the National Key R&D Program of China(2020YFA0707600)the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2016-I2M-1-014 to J.W.).
文摘SARS-CoV-2 is the pathogenic agent of COVID-19,which has evolved into a global pandemic.Compared with some other respiratory RNA viruses,SARS-CoV-2 is a poor inducer of type Ⅰ interferon(IFN).Here,we report that SARS-CoV-2 nsp12,the viral RNA-dependent RNA polymerase(RdRp),suppresses host antiviral responses.SARS-CoV-2 nsp12 attenuated Sendai virus(SeV)-or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner.It also inhibited IFN promoter activation triggered by RIG-I,MDA5,MAVS,and IRF3 overexpression.Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3.Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12.Given these findings,our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.
文摘In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).
基金This work was supported by the National Key R&D Program of China(grant numbers 2017YFC1200303 and 2016YFC1200701)by a China Special Grant for the Prevention and Control of Infectious Diseases(grant number 2017ZX10303401).
文摘With the profound changes in the international security situation,the progression of globalization,and the continuous advancement of biotechnology,the risks and challenges posed by major infectious diseases and bioterrorism to the international community are also increasing.Biosafety,therefore,presents new opportunities for international cooperation and global governance.The world has become more integrated and now shares a common destiny in terms of biosafety.In the face of the current risks and challenges,the international community must work together to avert threats,advance mutual interests,and safeguard global biosecurity.In the context of the current situation regarding biosafety and biosecurity,we conducted the present analysis,and present here some appropriate countermeasures.
基金supported by the National Natural Science Foundation of China(No.82200009)the National Key Research and Development Program of China(No.2021YFC0864700)+1 种基金the National Natural Science Foundation of China(No.81930063)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS No.2021-I2M-1-048).
文摘Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the n
基金supported by grants from the National Natural Science Foundation of China (31311120063,81470096,31570026,31471253)the Ministry of Education and Science of the Russian Federation (Chinese-Russian project:RFMEFI61315X0045)+3 种基金the intramural special grant for influenza virus research from the Chinese Academy of Sciences (KJZD-EW-L09)the IDRCAPEIR program (106915-001)Special Project of Ministry of Science and Technology (2013FY113500)supported by the “Taishan Scholar” project of Shandong Province
文摘A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.
文摘The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guerin （BCG） booster vaccination in China was estimated using tuberculin skin testing （TST） and QuantiFERON-TB Gold assay （QFT） to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5-15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST （induration ≥ 10 mm） and QFT positivity were 9.3% （264/2827） and 2.5% （71/2831）, respectively. The rate of QFT indeterminate result was 2.2% （62/2831）. The overall agreement between TST and QFT was low （concordance = 88.0%; K coefficient = 0.125）. Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26-2.31 ]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a two- step approach might be considered for TB infection testing among adolescents in China.
基金supported by grants from the Beijing Academy of Agriculture and ForestrSy cience (KJCX20230411 and KJCX20230211)National Natural Science Foundation of China (NSFC T2225005,22050004,21927802,21974069)+1 种基金Ministry of Science and Technology of the People's Republic of China (2018YFA0800200)Open Fund Programs of Shenzhen1 Bay Laboratory (SZBL2020090501001).
文摘The coronavirus disease of 2019(COVID‐19),a global pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),can result in severe health complications.In addition to physical preventative measures,pharmaceutical intervention is also crucial.Numerous natural products from medicinal fungi have shown promise as potential antiviral drugs and may serve as a source of effective components with antiviral activity against SARS‐CoV‐2 and other coronaviruses.In this study,we developed a workflow that integrates viral infection inhibition assays at both cellular and molecular levels,as well as molecular separation and characterization,to screen and identify natural products with antiviral activity.Using this workflow,we screened 167 extracts extracted from 36 medicinal fungi using optimized extraction methods.We assessed the antiviral effects of these extracts by measuring their ability to inhibit SARS‐CoV‐2 infection and receptor binding domain‐human angiotensin‐converting enzyme 2(RBD‐hACE2)binding in vitro.Following charge‐and size‐based characterization of the active compounds through filtration and chromatographic fractionation,mass spectrometry characterization of the fractionated compounds revealed that the active components are polysaccharides and determined their monosaccharide residue composition.Our findings provide new insights into the antiviral potential of natural products and their screening strategies and may contribute to the development of effective antiviral therapeutics against COVID‐19 and other diseases.
