B******n
发帖数: 1920 | 1 https://vetmed.umn.edu/bio/college-of-veterinary-medicine/fang-li
十年从NIH拿了500万
Grants for Grant R01AI089728
Receptor recognition and cell entry of coronaviruses
Receptor recognition and cell entry by viruses are two initial and essential
steps in viral infection cycles. They are important determinants of viral
host ranges, tissue tropisms and pathogenesis, and are primary targets for
human intervention. Coronaviruses (CoVs) pose serious health threats to
humans and other animals. SARS-CoV and MERS-CoV have infected thousands of
people with significant fatality, whereas porcine epidemic diarrhea CoV is
currently causing ~100% fatality in piglets. A virus-surface spike protein
guides CoV entry into host cells by binding to its host receptor via its S1
subunit and fusing viral and host membranes via its S2 subunit. S1 from
different CoVs recognizes a variety of host receptors through one or both of
its domains (S1-NTD and S1-CTD), and the S1/S2 boundary is cleaved by host
proteases for activation of membrane fusion by S2. Our previous research has
determined a number of crystal structures of CoV S1 domains by themselves
or in complex with their respective receptor, and also shown how proteolysis
regulates the cell entry of some CoVs. Our research has contributed
critically to the current knowledge about the molecular mechanisms for CoV
receptor recognition, cell entry, and cross-species transmission. In this
competitive renewal of R01, we will continue to investigate how CoVs exploit
host receptors and host proteases for cell entry. This proposal has three
specific aims. Aim 1 examines receptor binding by CoV S1-NTDs. Specifically,
we will investigate whether S1-NTDs from different CoV genera have the same
structural fold and evolutionary origin as host galectins (galactose-
binding lectins). We will also examine how CoV S1-NTDs recognize sugar
receptors. These studies will reveal the evolutionary origins of CoV S1-NTDs
, enhance understanding of sugar recognition by CoVs, and may facilitate
future design of sugar analogues and subunit vaccines to inhibit CoV
infections. Aim 2 focuses on receptor binding by CoV S1-CTDs. Specifically,
we will analyze the interactions between the S1-CTDs of bat SARS-like CoVs (
SL-CoVs) and the protein receptor homologues from humans and other animals,
and elucidate how bat SL-CoVs transmitted to humans and other animals to
cause the SARS epidemic through evolutionary changes in their S1-CTDs. These
studies will provide critical information for understanding emergence
potential of bat SL-CoVs and for facilitating epidemic monitoring and
control. Aim 3 investigates cell entry by CoVs. Specifically, we will
investigate what host proteases activate CoV entry and how the proteases
motifs in CoV spikes have evolved to modulate CoV entry. These studies will
reveal how host proteases regulate CoV entry to meet their specific need for
host range, tissue tropism and pathogenesis, and may facilitate future
design of protease inhibitors to block CoV entry. Overall, this proposal
investigates the molecular and structural mechanisms for receptor
recognition, cell entry, cross-species transmission, and tissue tropism of
CoVs, which will lead to novel principles in virology. This research is also
important for evaluating the emerging disease potentials of CoVs and for
preventing, controlling and treating CoV infections in humans and other
animals.
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2019-06-01 2020-05-31 $455,796 $455,
796
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2019-06-01 2020-05-31 $455,796 $455,
796
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2018-06-01 2019-05-31 $455,615
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2017-06-01 2018-05-31 $453,437
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2017-06-01 2018-05-31 $453,437
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2017-06-01 2018-05-31 $453,437
Receptor Recognition And Cell Entry Of Coronaviruses University Of
Minnesota Li, Fang 2016-06-07 2017-05-31 $464,440
Receptor Recognition Mechanisms Of Coronaviruses University Of Minnesota
Li, Fang 2014-05-01 2015-04-30 $373,725
Receptor Recognition Mechanisms Of Coronaviruses University Of Minnesota
Li, Fang 2013-05-01 2014-04-30 $351,302
Receptor Recognition Mechanisms Of Coronaviruses University Of Minnesota
Li, Fang 2012-05-01 2013-04-30 $373,725
Receptor Recognition Mechanisms Of Coronaviruses University Of Minnesota
Li, Fang 2011-05-01 2012-04-30 $373,725
Receptor Recognition Mechanisms Of Coronaviruses University Of Minnesota
Li, Fang 2010-05-15 2011-04-30 $377,500
Literature (1)
Authors (1) | m********i
发帖数: 5 | 2 基金大亨
essential
【在 B******n 的大作中提到】
: https://vetmed.umn.edu/bio/college-of-veterinary-medicine/fang-li
: 十年从NIH拿了500万
: Grants for Grant R01AI089728
: Receptor recognition and cell entry of coronaviruses
: Receptor recognition and cell entry by viruses are two initial and essential
: steps in viral infection cycles. They are important determinants of viral
: host ranges, tissue tropisms and pathogenesis, and are primary targets for
: human intervention. Coronaviruses (CoVs) pose serious health threats to
: humans and other animals. SARS-CoV and MERS-CoV have infected thousands of
: people with significant fatality, whereas porcine epidemic diarrhea CoV is
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