This paper concerns the existence of multiple homoclinic orbits for the second-order Hamiltonian system-L（t）z＋Wz（t,z）=0,where L∈C（R,RN2）is a symmetric matrix-valued function and W（t,z）∈C1（R×RN,R）is a...This paper concerns the existence of multiple homoclinic orbits for the second-order Hamiltonian system-L（t）z＋Wz（t,z）=0,where L∈C（R,RN2）is a symmetric matrix-valued function and W（t,z）∈C1（R×RN,R）is a nonlinear term.Since there are no periodic assumptions on L（t）and W（t,z）in t,one should overcome difficulties for the lack of compactness of the Sobolev embedding.Moreover,the nonlinearity W（t,z）is asymptotically linear in z at infinity and the system is allowed to be resonant,which is a case that has never been considered before.By virtue of some generalized mountain pass theorem,multiple homoclinic orbits are obtained.展开更多
Bat coronavirus(CoV)RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among all known coronaviruses,and also uses human angiotensin converting enzyme 2(...Bat coronavirus(CoV)RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among all known coronaviruses,and also uses human angiotensin converting enzyme 2(hACE2)for virus entry.Thus,SARS-CoV-2 is thought to have originated from bat.However,whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive.Here,we found that Rhinolophus affinis bat ACE2(Ra ACE2)is an entry receptor for both SARSCoV-2 and Ra TG13,although the binding of Ra ACE2 to the receptor-binding domain(RBD)of SARSCoV-2 is markedly weaker than that of h ACE2.We further evaluated the receptor activities of ACE2 s from additional 16 diverse animal species for Ra TG13,SARS-CoV,and SARS-CoV-2 in terms of S protein binding,membrane fusion,and pseudovirus entry.We found that the Ra TG13 spike(S)protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2,and seven out of sixteen different ACE2 s function as entry receptors for all three viruses,indicating that all three viruses might have broad host rages.Of note,Ra TG13 S pseudovirions can use mouse,but not pangolin ACE2,for virus entry,whereas SARS-CoV-2 S pseudovirions can use pangolin,but not mouse,ACE2 enter cells efficiently.Mutagenesis analysis revealed that residues 484 and 498 in Ra TG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2 s.Finally,two polymorphous Rhinolophous sinicus bat ACE2 s showed different susceptibilities to virus entry by Ra TG13 and SARS-CoV-2 S pseudovirions,suggesting possible coevolution.Our results offer better understanding of the mechanism of coronavirus entry,host range,and virushost coevolution.展开更多
文摘This paper concerns the existence of multiple homoclinic orbits for the second-order Hamiltonian system-L（t）z＋Wz（t,z）=0,where L∈C（R,RN2）is a symmetric matrix-valued function and W（t,z）∈C1（R×RN,R）is a nonlinear term.Since there are no periodic assumptions on L（t）and W（t,z）in t,one should overcome difficulties for the lack of compactness of the Sobolev embedding.Moreover,the nonlinearity W（t,z）is asymptotically linear in z at infinity and the system is allowed to be resonant,which is a case that has never been considered before.By virtue of some generalized mountain pass theorem,multiple homoclinic orbits are obtained.
基金supported by the National Key R&D Program of China(2020YFA0707600 and 2020YFC0841000)the National Natural Science Foundation of China(31970171 and 31670164)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2016-12M-1-014 and 2020-12M-Co V19-010)。
文摘Bat coronavirus(CoV)RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)among all known coronaviruses,and also uses human angiotensin converting enzyme 2(hACE2)for virus entry.Thus,SARS-CoV-2 is thought to have originated from bat.However,whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive.Here,we found that Rhinolophus affinis bat ACE2(Ra ACE2)is an entry receptor for both SARSCoV-2 and Ra TG13,although the binding of Ra ACE2 to the receptor-binding domain(RBD)of SARSCoV-2 is markedly weaker than that of h ACE2.We further evaluated the receptor activities of ACE2 s from additional 16 diverse animal species for Ra TG13,SARS-CoV,and SARS-CoV-2 in terms of S protein binding,membrane fusion,and pseudovirus entry.We found that the Ra TG13 spike(S)protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2,and seven out of sixteen different ACE2 s function as entry receptors for all three viruses,indicating that all three viruses might have broad host rages.Of note,Ra TG13 S pseudovirions can use mouse,but not pangolin ACE2,for virus entry,whereas SARS-CoV-2 S pseudovirions can use pangolin,but not mouse,ACE2 enter cells efficiently.Mutagenesis analysis revealed that residues 484 and 498 in Ra TG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2 s.Finally,two polymorphous Rhinolophous sinicus bat ACE2 s showed different susceptibilities to virus entry by Ra TG13 and SARS-CoV-2 S pseudovirions,suggesting possible coevolution.Our results offer better understanding of the mechanism of coronavirus entry,host range,and virushost coevolution.
