Whole viral particle dynamics
Viral protein dynamics throughout virus life cycle
Our lab works on multiple different viral systems, highlighting viral protein dynamics throughout distinct lifecycle phases. To read more about the viruses we work on and how we use biophysical techniques to determine protein dynamics, click on the phase or scroll down for more information.
Virus breathing and antibody recognition
We study the viral breathing patterns of 3 different viruses: Coxsackievirus, HPV16, and dengue.
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The dynamics of coxsackievirus are being mapped by antibody binding and HDX-MS at varying temperatures to identify cryptic epitopes. This will allow for more efficient targeting of antiviral agents.
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HPV16 consists of 2 capsid proteins, one of which remains unstructured. Through antibody binding, HDX-MS, and limited proteolysis-MS we are mapping the dynamics of the unstructured protein to verify regions that sit outside the viral capsid.
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Dengue virus exhibits reversible expanding and contracting to sense pH, temperature, and osmolarity, allowing for receptor binding. We are able to map these reversible conformational changes within the whole viral particle by HDX-MS to understand the environmental sensing essential for genomic transport and release.
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For further reading on viral breathing and antibody binding, check out our publications
Lim XX, Shu B, Zhang S, et al. Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics. Cell. 2021;184(25):6067-6080.e13.​​​
Lim XX, Chandramohan A, Lim XY, Bag N, Sharma KK, Wirawan M, Wohland T, Lok SM, Anand GS. Conformational changes in intact dengue virus reveal serotype-specific expansion. Nature Communications. 2017 Feb 10;8:14339.
Receptor binding
Our lab focuses on the receptor binding pathway for 3 different viruses: SARS-CoV-2 and Coxsackievirus
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Our lab has previously reported the SARS-CoV-2 spike protein interactions with receptor ACE2 and are continuing to monitor the effects of variant mutations on SARS-CoV-2 cell entry, from ACE2 binding to genomic release.​​
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We are currently working to map the receptor binding interface and allosteric effects by doing HDX-MS on coxsackievirus bound to it's receptor, CAR and its secondary receptor, DAF.
SARS-CoV-2 spike (S) protein
For further reading on receptor binding, check out our publications
Sean M Braet, Theresa SC Buckley, Varun Venkatakrishnan, Kim-Marie A Dam, Pamela J Bjorkman, Ganesh S Anand. Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics. eLife. 2023. 12:e82584
Palur V Raghuvamsi, Nikhil K Tulsian, Firdaus Samsudin, Xinlei Qian, Kiren Purushotorman, Gu Yue, Mary M Kozma, Wong Y Hwa, Julien Lescar, Peter J Bond, Paul A MacAry, Ganesh S Anand. SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets. eLife. 2021. 10:e63646
Endosome entry
We employ HDX-MS to monitor the effects of endosomal pH changes on coxsackievirus and adeno-associated virus (AAV).
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To monitor the effects of pH changes on viral particles as they are trafficked through the cell by endosomes, our lab employs HDX-MS to track conformational changes within coxsackievirus and adeno associated virus (AAV) that allow the virus to eventually escape the endosome to be replicated.
Adeno associate virus (AAV)
PDB:7NA6
Assembly and maturation
Our lab has focused on the assembly and maturation processes for two key viruses, turnip crinkle virus (TCV) and SARS-CoV-2.
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Our research has pioneered structural mass spectrometry characterization of temperature and divalent cation-dependent conformational changes on Turnip Crinkle Virus (TCV) and mapped the specific disassembly process.
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SARS-CoV-2 must go through a maturation process within the Golgi prior to cellular release that includes furin cleavage of the spike protein. While furin cleavage may also occur at the cell surface prior to cellular entry, it is known that furin also cleaves Spike prior to virion release. Our lab is focusing on mapping the furin:spike protein interface to monitor effects of variant mutation on furin cleavage efficiency.
Spike (S) protein
ACE2
For further reading on viral assembly and maturation, check out our publications
Ramesh R, Lim XX, Raghuvamsi PV, Wu C, Wong SM, Anand GS. Uncovering metastability and disassembly hotspots in whole viral particles. Prog Biophys Mol Biol. 2019 May;143:5-12. doi: 10.1016/j.pbiomolbio.2018.12.006. Epub 2018 Dec 13. PMID: 30553754.