Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 l...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 linage,which was first detected in Indonesia on 17 February 2023,has raised concerns due to its increased prevalence and extended immune escape properties,according to the risk analysis by the World Health Organization(WHO)[1].As of 3 October 2023,EG.5 and its sub-linages have been reported in 83 countries with shared 49,008 genome sequences in GISAID database(https://gisaid.org/hcov19-variants/).EG.5 has become the dominant strain in the United States according to Centers for Disease Control and Prevention(CDC),accounting for 29.4%of SARS-CoV-2 infections(https://covid.cdc.gov/covid-data-tracker/#variant-proportions).展开更多
Coronaviruses(Co Vs)have brought serious threats to humans,particularly severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which continually evolves into multiple variants.These variants,especially Omicron,r...Coronaviruses(Co Vs)have brought serious threats to humans,particularly severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which continually evolves into multiple variants.These variants,especially Omicron,reportedly escape therapeutic antibodies and vaccines,indicating an urgent need for new antivirals with pan-SARS-Co V-2 inhibitory activity.We previously reported that a peptide fusion inhibitor,P3,targeting heptad repeated-1(HR1)of SARS-Co V-2 spike(S)protein,could inhibit viral infections.Here,we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative,the P315V3,showed the most efficient antiviral activity against SARS-Co V-2 variants and several other sarbecoviruses,as well as other human-Co Vs(HCo Vs).P315V3 also exhibited effective prophylactic efficacy against the SARS-Co V-2 Delta and Omicron variants in mice via intranasal administration.These results suggest that P315V3,which is in PhaseⅡclinical trial,is promising for further development as a nasal pan-SARS-Co V-2 or pan-Co Vs inhibitor to prevent or treat CoV diseases.展开更多
With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as ...With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.展开更多
Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human health.However,it remains unclear whether the currently available va...Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human health.However,it remains unclear whether the currently available vaccines are effective against these coronaviruses.Here,we constructed a wild-type mouse model to evaluate pathogenicity of the SARS-CoV-2-related pangolin coronavirus GX/P2V/2017 and neutralization efficacy of the approved tandemrepeat SARS-CoV-2 spike receptor-binding domain(RBD)vaccine ZF2001.We found that ZF2001-induced cross-reactive and cross-neutralizing antibodies against GX/P2V/2017,and the vaccination alleviated the pathological lung damage caused by GX/P2V/2017 in mice.These results indicate that RBD may work as a promising candidate for pan-coronavirus vaccine development.展开更多
Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is a great threat to global public health.Although several vaccines and therapeutic anti...Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is a great threat to global public health.Although several vaccines and therapeutic antibodies have been authorized for emergency use,several studies have reported that they show weakened protective effects against SARS-CoV-2 variants,including Alpha,Beta,Gamma,and currently dominant Delta and Lambda.展开更多
基金supported by the National Key R&D Program of China(2023YFC0871300 and 2022YFC2303403)the National Natural Science Foundation of China(82225021)Q.W.is supported by the Chinese Academy of Sciences(YSBR-010 and Y2022037).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to pose a significant threat to the world,as it continually evolves and gives rise to multiple variants and sub-variants.Recently,the Omicron EG.5 linage,which was first detected in Indonesia on 17 February 2023,has raised concerns due to its increased prevalence and extended immune escape properties,according to the risk analysis by the World Health Organization(WHO)[1].As of 3 October 2023,EG.5 and its sub-linages have been reported in 83 countries with shared 49,008 genome sequences in GISAID database(https://gisaid.org/hcov19-variants/).EG.5 has become the dominant strain in the United States according to Centers for Disease Control and Prevention(CDC),accounting for 29.4%of SARS-CoV-2 infections(https://covid.cdc.gov/covid-data-tracker/#variant-proportions).
基金supported by the National Key R&D Program of China(2022YFC2303403)the National Natural Science Foundation of China(82225021 and 32171428)the CAS Young Scientists in Basic Research(YSBR-010)。
基金the Ministry of Science and Technology of the People’s Republic of China(2023YFC0871300 and 2022YFC2604103)the National Natural Science Foundation of China(82225021)+3 种基金Science and Technology Program of Shenzhen,China(JSGG20220606140800001)Research&Development Project in Key Areas of Guangdong Province(2022B1111060001)the Science and Technology Planning Project of Guangdong Province of China(2021B1212030009)the Chinese Academy of Sciences(YSBR-010 and Y2022037)。
文摘Coronaviruses(Co Vs)have brought serious threats to humans,particularly severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which continually evolves into multiple variants.These variants,especially Omicron,reportedly escape therapeutic antibodies and vaccines,indicating an urgent need for new antivirals with pan-SARS-Co V-2 inhibitory activity.We previously reported that a peptide fusion inhibitor,P3,targeting heptad repeated-1(HR1)of SARS-Co V-2 spike(S)protein,could inhibit viral infections.Here,we further designed multiple derivatives of the P3 based on structural analysis and found that one derivative,the P315V3,showed the most efficient antiviral activity against SARS-Co V-2 variants and several other sarbecoviruses,as well as other human-Co Vs(HCo Vs).P315V3 also exhibited effective prophylactic efficacy against the SARS-Co V-2 Delta and Omicron variants in mice via intranasal administration.These results suggest that P315V3,which is in PhaseⅡclinical trial,is promising for further development as a nasal pan-SARS-Co V-2 or pan-Co Vs inhibitor to prevent or treat CoV diseases.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(grant number XDB29040203)the National Key Research and Development Program of China(grant number 2021YFA1301404 and 2020YFA0907102)+2 种基金the National Natural Science Foundation of China(grant numbers 82225021 and 32171428)In addition,Qihui Wang was supported by the CAS Project for Young Scientists in Basic Research(grant number YSBR-010)the Youth Innovation Promotion Association of the CAS(grant number Y2022037).We thank Professor Xiao Zhao from the National Center for Nanoscience and Technology for sharing the LNP encapsulation and DLS platforms.We thank Dr.Kun Xu for his help during the revision of this manuscript.We thank Linjie Li for sharing recombinant RBD proteins.We thank the Institutional Center for Shared Technology and Facilitates in the Institute of Microbiology,CAS,and the Institute of Zoology,CAS.
文摘With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.
基金supported by the National Key R&D Program of China(2022YFC2303403 and 2021YFC0863400)the National Natural Science Foundation of China(NSFC 82225021 and 32000127)+1 种基金Q.W.is supported by the Youth Innovation Promotion Association CAS(Y2022037)G.F.G.is supported by the Yanqi Lake Meeting organized by the Academic Divisions of CAS.
文摘Many severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)–related coronaviruses have been discovered,constituting potential threats to human health.However,it remains unclear whether the currently available vaccines are effective against these coronaviruses.Here,we constructed a wild-type mouse model to evaluate pathogenicity of the SARS-CoV-2-related pangolin coronavirus GX/P2V/2017 and neutralization efficacy of the approved tandemrepeat SARS-CoV-2 spike receptor-binding domain(RBD)vaccine ZF2001.We found that ZF2001-induced cross-reactive and cross-neutralizing antibodies against GX/P2V/2017,and the vaccination alleviated the pathological lung damage caused by GX/P2V/2017 in mice.These results indicate that RBD may work as a promising candidate for pan-coronavirus vaccine development.
基金This work was supported by the Ministry of Science and Technology of the People’s Republic of China(2021YFC0863300)the National Key Research and Development Program of China(2020YFA0509202)the Strategic Priority Research Program of CAS(XDB29040203).
文摘Dear Editor,The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is a great threat to global public health.Although several vaccines and therapeutic antibodies have been authorized for emergency use,several studies have reported that they show weakened protective effects against SARS-CoV-2 variants,including Alpha,Beta,Gamma,and currently dominant Delta and Lambda.
