Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2
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.
1 S10 RR025660-01A1
National Institute of Allergy and Infectious Diseases
glycodendrimers, HIV-1, molecular dynamics, SARS-CoV-2 receptor binding domain
Lauren Wells, Cory Vierra, Janee’ Hardman, Yanxiao Han, Dustin Dimas, Lucia N. Gwarada-Phillips, Rachel Blackeye, Daryl K. Eggers, Celia C. LaBranche, Petr Král, and Katherine D. McReynolds. "Sulfoglycodendrimer Therapeutics for HIV-1 and SARS-CoV-2" Advanced Therapeutics (2021). https://doi.org/10.1002/adtp.202000210