Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2

Overview

Journal Adv Ther (Weinh)

Date 2021 Mar 31

PMID 33786368

Citations 4

Authors

Lauren Wells

Cory Vierra

Janee Hardman

Yanxiao Han

Dustin Dimas

Lucia N Gwarada-Phillips

Rachel Blackeye

Daryl K Eggers

Celia C LaBranche

Petr Kral

Katherine D McReynolds

Affiliations

Soon will be listed here.

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.

Citing Articles

Sulfoglycodendron Antivirals with Scalable Architectures and Activities.

Coppola F, Jafari R, McReynolds K, Kral P J Chem Inf Model. 2024; 64(18):7141-7151.

PMID: 39230262 PMC: 11498201. DOI: 10.1021/acs.jcim.4c00541.

Sulfoglycodendron Antivirals with Scalable Architectures and Activities.

Coppola F, Jafari R, McReynolds K, Kral P bioRxiv. 2024; .

PMID: 39131386 PMC: 11312539. DOI: 10.1101/2024.08.01.606251.

Synthesis and Nuclear Magnetic Resonance Structural Evaluation of Oxime-Linked Oligosialic Acid-Based Glycodendrimers.

Cerney J, Raskovalov A, Nasseri M, Silva M, McReynolds K Biomacromolecules. 2023; 24(4):1901-1911.

PMID: 36989087 PMC: 10091409. DOI: 10.1021/acs.biomac.3c00105.

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor.

Jeong W, Bu J, Mickel P, Han Y, Rawding P, Wang J Biomacromolecules. 2022; 24(1):141-149.

PMID: 36562668 PMC: 9811402. DOI: 10.1021/acs.biomac.2c01018.

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