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Sulfoglycodendrimer Therapeutics for HIV‐1 and SARS‐CoV‐2
Author(s) -
Wells Lauren,
Vierra Cory,
Hardman Janee’,
Han Yanxiao,
Dimas Dustin,
GwaradaPhillips Lucia N.,
Blackeye Rachel,
Eggers Daryl K.,
LaBranche Celia C.,
Král Petr,
McReynolds Katherine D.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202000210
Subject(s) - glycoprotein , covid-19 , human immunodeficiency virus (hiv) , binding site , heparan sulfate , virology , chemistry , cell , biology , biochemistry , medicine , infectious disease (medical specialty) , disease , pathology
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.