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HGNC Genes

SARS-CoV-2 proteins

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    Exploring the role of glycans in the interaction of SARS-CoV-2 RBD MESHD and human receptor ACE2

    Authors: Kien Nguyen; Srirupa Chakraborty; Rachael Mansbach; Bette Korber; S. Gnanakaran

    doi:10.1101/2021.03.30.437783 Date: 2021-03-31 Source: bioRxiv

    COVID-19 MESHD is a highly infectious respiratory disease MESHD caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2 HGNC, enabling the virus to enter the host cell. Both the Spike and ACE2 HGNC are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2 HGNC. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD- ACE2 HGNC complex without glycans, (ii) RBD- ACE2 HGNC with oligomannose MAN9 HGNC glycans in ACE2 HGNC, and (iii) RBD- ACE2 HGNC with complex FA2 HGNC glycans in ACE2 HGNC. These simulations identify the key residues at the RBD- ACE2 HGNC interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD- ACE2 HGNC contact signature is not altered by the presence of different glycoforms, suggesting that RBD- ACE2 HGNC interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 HGNC that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 HGNC can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 HGNC glycans on ACE2 HGNC decrease RBD- ACE2 HGNC affinity, while FA2 HGNC glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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