A 72-h high-resolution simulation of Supertyphoon Rammasun (2014) is performed using the Advanced Research Weather Research and Forecasting model. The model covers an initial 18-h spin-up, the 36-h rapid intensifica...A 72-h high-resolution simulation of Supertyphoon Rammasun (2014) is performed using the Advanced Research Weather Research and Forecasting model. The model covers an initial 18-h spin-up, the 36-h rapid intensification (RI) period in the northern South China Sea, and the 18-h period of weakening after landfall. The results show that the model reproduces the track, intensity, structure of the storm, and environmental circulations reasonably well. Analysis of the surface energetics under the storm indicates that the storm's intensification is closely related to the net energy gain rate (eg), defined as the difference between the energy production (PD) due to surface entropy flux and the energy dissipation (Ds) due to surface friction near the radius of maximum wind (RMW). Before and during the RI stage, the ~:g is high, indicating sufficient energy supply for the storm to intensify. However, the Sg decreases rapidly as the storm quickly intensifies, because the Ds increases more rapidly than the PD near the RMW. By the time the storm reaches its peak intensity, the Ds is about 20% larger than the PD near the RMW, leading to a local energetics deficit under the eyewall. During the mature stage, the PD and Ds can reach a balance within a radius of 86 km from the storm center (about 2.3 times the RMW). This implies that the local PD under the eyewall is not large enough to balance the Ds, and the radially inward energy transport from outside the eyewall must play an important role in maintaining the storm's intensity, as well as its intensification.展开更多
Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant ade...Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant adenovirus vector vaccines and protein subunit vaccines,have been licensed and have achieved tremendous success in preventing infections,particularly severe hospitalization and death(Feikin et al.,2022;Ssentongo et al.,2022).However,with the emergence of new variants,breakthrough infections have occurred among vaccines,highlighting the need to develop broad-spectrum vaccines(Ukwishaka et al.,2023).展开更多
During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has beco...During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 i...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.展开更多
The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing a...The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies(bnAbs).Here,we developed a panel of bnAbs against Omicron and other variants of concern(VOCs)elicited by vaccination of adenovirus-vectored COVID-19 vaccine(Ad5-nCoV).展开更多
Antibodies are ideal for controlling the influenza A virus,but their effect on newly emerging strains is unclear.Here,we assessed the neutralization activity of the humanized monoclonal antibodies(mAbs)F10,H98 and H40...Antibodies are ideal for controlling the influenza A virus,but their effect on newly emerging strains is unclear.Here,we assessed the neutralization activity of the humanized monoclonal antibodies(mAbs)F10,H98 and H40 against circulating influenza viruses(H5N1,H1N1,H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9).The results showed that all the three humanized mAbs(F10,H98 and H40)displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses.Remarkably,the humanized monoclonal antibody F10 produced higher and broader neutralization titers(range 25–1.56μg/ml)than those of the other two humanized mAbs(H98(range 50–3.12μg/ml),H40(range 50–5.56μg/ml))to against the viruses H5N1,H1N1,H3N2,H7N7,H5N6 and H7N9.This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.展开更多
基金supported by the National Basic Research and Development Project (973 program) of China (Grant No. 2015CB452805)the National Natural Science Foundation of China (Grant No. 41375068)partly supported by the National Science Foundation (Grant No. AGS-1326524)
文摘A 72-h high-resolution simulation of Supertyphoon Rammasun (2014) is performed using the Advanced Research Weather Research and Forecasting model. The model covers an initial 18-h spin-up, the 36-h rapid intensification (RI) period in the northern South China Sea, and the 18-h period of weakening after landfall. The results show that the model reproduces the track, intensity, structure of the storm, and environmental circulations reasonably well. Analysis of the surface energetics under the storm indicates that the storm's intensification is closely related to the net energy gain rate (eg), defined as the difference between the energy production (PD) due to surface entropy flux and the energy dissipation (Ds) due to surface friction near the radius of maximum wind (RMW). Before and during the RI stage, the ~:g is high, indicating sufficient energy supply for the storm to intensify. However, the Sg decreases rapidly as the storm quickly intensifies, because the Ds increases more rapidly than the PD near the RMW. By the time the storm reaches its peak intensity, the Ds is about 20% larger than the PD near the RMW, leading to a local energetics deficit under the eyewall. During the mature stage, the PD and Ds can reach a balance within a radius of 86 km from the storm center (about 2.3 times the RMW). This implies that the local PD under the eyewall is not large enough to balance the Ds, and the radially inward energy transport from outside the eyewall must play an important role in maintaining the storm's intensity, as well as its intensification.
文摘Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has posed a continuous threat to global public health.A number of vaccines,such as inactivated vaccines,mRNA vaccines,recombinant adenovirus vector vaccines and protein subunit vaccines,have been licensed and have achieved tremendous success in preventing infections,particularly severe hospitalization and death(Feikin et al.,2022;Ssentongo et al.,2022).However,with the emergence of new variants,breakthrough infections have occurred among vaccines,highlighting the need to develop broad-spectrum vaccines(Ukwishaka et al.,2023).
基金supported by China Natural Science Foundation (82150201)
文摘During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.
基金This work was jointly supported by the Natural Science Foundation of Hubei Province of China(2019CFA076)the National Natural Science Foundation of China(32170949).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.
基金We thank the cryo-EM facility and the High-Performance Computing Center of Westlake University for providing technical support.We thank the Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,China,for providing the SARS-CoV-2.This research was supported by grants from the National Natural Science Foundation of China(projects 32022037,81803429)the Young Elite Scientists Sponsorship Program by CAST,the Leading Innovative and Entrepreneur Team Introduction Program of Hangzhou,the Special Research Program of Novel Coronavirus Pneumonia of Westlake University and Tencent Foundation.
文摘The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies(bnAbs).Here,we developed a panel of bnAbs against Omicron and other variants of concern(VOCs)elicited by vaccination of adenovirus-vectored COVID-19 vaccine(Ad5-nCoV).
基金This work was supported by the National Key Research and Development Program of China(2017YFD0501705 and 2016YFD0500203).
文摘Antibodies are ideal for controlling the influenza A virus,but their effect on newly emerging strains is unclear.Here,we assessed the neutralization activity of the humanized monoclonal antibodies(mAbs)F10,H98 and H40 against circulating influenza viruses(H5N1,H1N1,H3N2 and H7N7 and new subtypes viruses H5N6 and H7N9).The results showed that all the three humanized mAbs(F10,H98 and H40)displayed different degrees of virus neutralization activities when encountered with different subtypes of influenza viruses.Remarkably,the humanized monoclonal antibody F10 produced higher and broader neutralization titers(range 25–1.56μg/ml)than those of the other two humanized mAbs(H98(range 50–3.12μg/ml),H40(range 50–5.56μg/ml))to against the viruses H5N1,H1N1,H3N2,H7N7,H5N6 and H7N9.This mAb may represent a new class of heterosubtypic neutralizing humanized mAb that could replace vaccines and chemical drugs.