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dc.contributor.author Wells, Lauren
dc.contributor.author Vierra, Cory
dc.contributor.author Hardman, Janee
dc.contributor.author Han, Yanxiao
dc.contributor.author Dimas, Dustin
dc.contributor.author Gwarada-Phillips, Lucia N.
dc.contributor.author Blackeye, Rachel
dc.contributor.author Eggers, Daryl K.
dc.contributor.author LaBranche, Celia C.
dc.contributor.author Král, Petr
dc.contributor.author McReynolds, Katherine D.
dc.date.accessioned 2021-03-24T20:06:09Z
dc.date.available 2021-03-24T20:06:09Z
dc.date.issued 2021-02-12
dc.identifier.issn 2366-3987
dc.identifier.uri http://hdl.handle.net/10211.3/218835
dc.description This is the peer reviewed version of the following article: Wells, L., Vierra, C., Hardman, J., Han, Y., Dimas, D., Gwarda-Phillips, L. N., et. al. (2021). Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2. Advanced Therapeutics. doi:https://doi.org/10.1002/adtp.202000210, which has been published in final form at https://doi.org/10.1002/adtp.202000210. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. en_US
dc.description.abstract Hexavalent sulfoglycodendrimers (SGDs) are synthesized as mimics of host cell heparan sulfate proteoglycans (HSPGs) to inhibit the early stages in viral binding/entry of HIV‐1 and SARS‐CoV‐2. Using an HIV neutralization assay, the most promising of the seven candidates are found to have sub‐micromolar anti‐HIV activities. Molecular dynamics simulations are separately implemented to investigate how/where the SGDs interacted with both pathogens. The simulations revealed that the SGDs: 1) develop multivalent binding with polybasic regions within and outside of the V3 loop on glycoprotein 120 (gp120) for HIV‐1, and consecutively bind with multiple gp120 subunits, and 2) interact with basic amino acids in both the angiotensin‐converting enzyme 2 (ACE2) and HSPG binding regions of the Receptor Binding Domain (RBD) from SARS‐CoV‐2. These results illustrate the considerable potential of SGDs as inhibitors in viral binding/entry of both HIV‐1 and SARS‐CoV‐2 pathogens, leading the way for further development of this class of molecules as broad‐spectrum antiviral agents. en_US
dc.description.sponsorship NIH‐SCORE 5SC3GM119521 (K.D.M.); NIAID‐NIH Contract Number: HHSN272201800004C (C.C.L.); NSF‐MRI (500 MHz NMR spectrometer, MPS‐0922676 (KDM); MST instrument DBI‐1427465 (D.K.E.)); CSUPERB (California State University Program for Education and Research in Biotechnology) Research Development Award (K.D.M.); UIC Center for Clinical and Translational Science (P.K. and Y.H.); UIC Dean's Scholar Fellowship (Y.H.); CSUS Department of Chemistry Russell‐Forkey summer research fellowship (L.W.). Mass spectrometry was conducted at The Ohio State University Campus Chemical Instrument Center (CCIC) and acknowledges the following support for this facility: NIH Award Number P30 CA016058, NIH Award Number 1 S10 RR025660‐01A1, and NIH Award Number Grant S10 OD018507. The HIV‐1 AC10.29 gp120 Avi‐His Recombinant Protein (Cat #: 13055) was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, from Dr. Xueling Wu. TZM‐bl cells were obtained from the NIH AIDS Reagent Program, as contributed by John Kappes and Xiaoyun Wu. R. Anthony Perez for creating the MST image in Figure 3. en_US
dc.format.extent 39 en_US
dc.language.iso en en_US
dc.publisher Wiley en_US
dc.relation.uri https://doi.org/10.1002/adtp.202000210 en_US
dc.subject glycodendrimers en_US
dc.subject HIV-1 en_US
dc.subject molecular dynamics en_US
dc.subject SARS‐CoV‐2 receptor binding domain en_US
dc.title Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2 en_US
dc.type Preprint en_US
dc.contributor.department Department of Chemistry en_US

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