Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role i...Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.展开更多
Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular carcino...Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular carcinoma.Prevention of mother-to-child transmission(MTCT)of HBV is most important to control hepatitis B because a vast majority of HBV acquisition in infancy will become chronic carriers.展开更多
The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)poses a major threat to global health.The high mortality rate reported during the early stage of the COVID-19 ...The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)poses a major threat to global health.The high mortality rate reported during the early stage of the COVID-19 pandemic resulted in panic among patients,including lactating mothers.1-3 The detection of SARS-CoV-2 RNA in breastmilk raised great concerns regarding the possibility of mother-tochild transmission(MTCT)of the virus.4 According to several reports on the presence of SARS-CoV-2 in breastmilk,some experts suggested that breastfeeding should be conducted with caution,while others recommended that,infants should be separated from their mother and breastfeeding should be discontinued.展开更多
Dear Editor,Since severe acute respiratory syndrome coronavirus 2(SARSCoV-2)RNA has been detected in human breastmilk,infants’safety with breastmilk feeding is of great concern for women with coronavirus disease 2019...Dear Editor,Since severe acute respiratory syndrome coronavirus 2(SARSCoV-2)RNA has been detected in human breastmilk,infants’safety with breastmilk feeding is of great concern for women with coronavirus disease 2019(COVID-19).1 It is known that milk has antiviral properties.2 However,little is known about the antiviral property of human breastmilk to SARS-CoV-2 and its related pangolin coronavirus(GX_P2V).Here we present for the first time that whey protein from human breastmilk effectively inhibited both SARS-CoV-2 and GX_P2V by blocking viral attachment and viral replication at entry and even post entry.Moreover,human whey protein inhibited infectious virus production,as proved by the plaque assay.We found that whey protein from different species,such as cow and goat,also showed anti-coronavirus properties.Commercial bovine formula milk also showed similar anti-SARS-CoV-2 activity.展开更多
基金supported by National Natural Science Foundation of China(Grant Nos.:81891010/81891011,81725023,82003614,82173950,31770192,32070187,32161133003 and 82003681)China Postdoctoral Science Foundation(Grant No:2022T150029).
文摘Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
基金This work was funded by the Health Commission of Nanjing City(ZKX20021)Science and Technology Department of Jiangsu Province(BK20221169)Jiangsu Province Center for Innovation in Obstetrics and Gynecology(CXZX202229),China.
文摘Chronic hepatitis B virus(HBV)infection,referred to the presence of hepatitis B surface antigen(HBsAg)over 6 months,is a serious health issue because of its severe sequelae such as cirrhosis and hepatocellular carcinoma.Prevention of mother-to-child transmission(MTCT)of HBV is most important to control hepatitis B because a vast majority of HBV acquisition in infancy will become chronic carriers.
文摘The coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)poses a major threat to global health.The high mortality rate reported during the early stage of the COVID-19 pandemic resulted in panic among patients,including lactating mothers.1-3 The detection of SARS-CoV-2 RNA in breastmilk raised great concerns regarding the possibility of mother-tochild transmission(MTCT)of the virus.4 According to several reports on the presence of SARS-CoV-2 in breastmilk,some experts suggested that breastfeeding should be conducted with caution,while others recommended that,infants should be separated from their mother and breastfeeding should be discontinued.
基金We thank Prof.Youchun Wang and Weijin Huang(National Institutes for Food and Drug Control,China)for sharing the pseudovirus of SARS-CoV-2.We thank Xiaoyun Liu(Peking University Health Science Center)for helpful discussion.K.X.and Y.-H.Z.declare grants from the National Natural Science Foundation of China[Grant No.81802002 and 81873579(to K.X.)81672002(to Y.-H.Z.)].K.X.declares grants from the Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation(Grant No.BMU2017YB001).Y.T.declares grants from the Funds for First-class Discipline Construction(XK1805),Key Project of Beijing University of Chemical Technology(No.XK1803-06),and Fundamental Research Funds for Central Universities(No.BUCTRC201917).H.F.declares grants from the Fundamental Research Funds for Central Universities(No.BUCTZY2022).
文摘Dear Editor,Since severe acute respiratory syndrome coronavirus 2(SARSCoV-2)RNA has been detected in human breastmilk,infants’safety with breastmilk feeding is of great concern for women with coronavirus disease 2019(COVID-19).1 It is known that milk has antiviral properties.2 However,little is known about the antiviral property of human breastmilk to SARS-CoV-2 and its related pangolin coronavirus(GX_P2V).Here we present for the first time that whey protein from human breastmilk effectively inhibited both SARS-CoV-2 and GX_P2V by blocking viral attachment and viral replication at entry and even post entry.Moreover,human whey protein inhibited infectious virus production,as proved by the plaque assay.We found that whey protein from different species,such as cow and goat,also showed anti-coronavirus properties.Commercial bovine formula milk also showed similar anti-SARS-CoV-2 activity.