Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance

Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, has begun to spread into many countries worldwide. While the prevalence of monkeypox in Central and Western Africa is well-known, the recent rise in the number of cases spread through intimate personal contact, particularly in the United S...

Full description

Bibliographic Details
Main Authors: Deling Shi, Peng He, Yuefan Song, Shuihong Cheng, Robert J. Linhardt, Jonathan S. Dordick, Lianli Chi, Fuming Zhang
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/18/5898
_version_ 1797484359122419712
author Deling Shi
Peng He
Yuefan Song
Shuihong Cheng
Robert J. Linhardt
Jonathan S. Dordick
Lianli Chi
Fuming Zhang
author_facet Deling Shi
Peng He
Yuefan Song
Shuihong Cheng
Robert J. Linhardt
Jonathan S. Dordick
Lianli Chi
Fuming Zhang
author_sort Deling Shi
collection DOAJ
description Monkeypox virus (MPXV), a member of the Orthopoxvirus genus, has begun to spread into many countries worldwide. While the prevalence of monkeypox in Central and Western Africa is well-known, the recent rise in the number of cases spread through intimate personal contact, particularly in the United States, poses a grave international threat. Previous studies have shown that cell-surface heparan sulfate (HS) is important for vaccinia virus (VACV) infection, particularly the binding of VACV A27, which appears to mediate the binding of virus to cellular HS. Some other glycosaminoglycans (GAGs) also bind to proteins on Orthopoxviruses. In this study, by using surface plasmon resonance, we demonstrated that MPXV A29 protein (a homolog of VACV A27) binds to GAGs including heparin and chondroitin sulfate/dermatan sulfate. The negative charges on GAGs are important for GAG–MPXV A29 interaction. GAG analogs, pentosan polysulfate and mucopolysaccharide polysulfate, show strong inhibition of MPXV A29–heparin interaction. A detailed understanding on the molecular interactions involved in this disease should accelerate the development of therapeutics and drugs for the treatment of MPXV.
first_indexed 2024-03-09T23:02:23Z
format Article
id doaj.art-d3a1ab7581164d71b1db04830514f8d3
institution Directory Open Access Journal
issn 1420-3049
language English
last_indexed 2024-03-09T23:02:23Z
publishDate 2022-09-01
publisher MDPI AG
record_format Article
series Molecules
spelling doaj.art-d3a1ab7581164d71b1db04830514f8d32023-11-23T18:00:48ZengMDPI AGMolecules1420-30492022-09-012718589810.3390/molecules27185898Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon ResonanceDeling Shi0Peng He1Yuefan Song2Shuihong Cheng3Robert J. Linhardt4Jonathan S. Dordick5Lianli Chi6Fuming Zhang7National Glycoengineering Research Center, Shandong University, Qingdao 266237, ChinaCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USACenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USACenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USACenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USACenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USANational Glycoengineering Research Center, Shandong University, Qingdao 266237, ChinaCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USAMonkeypox virus (MPXV), a member of the Orthopoxvirus genus, has begun to spread into many countries worldwide. While the prevalence of monkeypox in Central and Western Africa is well-known, the recent rise in the number of cases spread through intimate personal contact, particularly in the United States, poses a grave international threat. Previous studies have shown that cell-surface heparan sulfate (HS) is important for vaccinia virus (VACV) infection, particularly the binding of VACV A27, which appears to mediate the binding of virus to cellular HS. Some other glycosaminoglycans (GAGs) also bind to proteins on Orthopoxviruses. In this study, by using surface plasmon resonance, we demonstrated that MPXV A29 protein (a homolog of VACV A27) binds to GAGs including heparin and chondroitin sulfate/dermatan sulfate. The negative charges on GAGs are important for GAG–MPXV A29 interaction. GAG analogs, pentosan polysulfate and mucopolysaccharide polysulfate, show strong inhibition of MPXV A29–heparin interaction. A detailed understanding on the molecular interactions involved in this disease should accelerate the development of therapeutics and drugs for the treatment of MPXV.https://www.mdpi.com/1420-3049/27/18/5898A29chondroitin sulfatedermatan sulfateheparinmonkeypox virussurface plasmon resonance
spellingShingle Deling Shi
Peng He
Yuefan Song
Shuihong Cheng
Robert J. Linhardt
Jonathan S. Dordick
Lianli Chi
Fuming Zhang
Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
Molecules
A29
chondroitin sulfate
dermatan sulfate
heparin
monkeypox virus
surface plasmon resonance
title Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
title_full Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
title_fullStr Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
title_full_unstemmed Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
title_short Kinetic and Structural Aspects of Glycosaminoglycan–Monkeypox Virus Protein A29 Interactions Using Surface Plasmon Resonance
title_sort kinetic and structural aspects of glycosaminoglycan monkeypox virus protein a29 interactions using surface plasmon resonance
topic A29
chondroitin sulfate
dermatan sulfate
heparin
monkeypox virus
surface plasmon resonance
url https://www.mdpi.com/1420-3049/27/18/5898
work_keys_str_mv AT delingshi kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT penghe kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT yuefansong kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT shuihongcheng kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT robertjlinhardt kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT jonathansdordick kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT lianlichi kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance
AT fumingzhang kineticandstructuralaspectsofglycosaminoglycanmonkeypoxvirusproteina29interactionsusingsurfaceplasmonresonance