Initial Recognition and Attachment of the Zika Virus to Host Cells: A Molecular Dynamics and Quantum Interaction Approach

• Published in: Chembiochem : a European journal of chemical biology Vol. 23; no. 21; pp. e202200351 - n/a
• Main Authors: Gómez, Santiago A., Rojas‐Valencia, Natalia, Gómez, Sara, Lans, Isaias, Restrepo, Albeiro
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 04.11.2022
• Subjects: Aedes; Aedes - metabolism; Animals; Bonding strength; Bridges; Cell membranes; Chondroitin sulfate; Disease transmission; Env protein; Fever; Glycosaminoglycans; Humans; Hydrogen bonding; Hydrogen bonds; Lysine; Molecular dynamics; Molecular Dynamics Simulation; Mosquitoes; Neurodegenerative diseases; Proteins; Receptors; Recognition; Salts; Sulfates; Vector-borne diseases; Viral envelope proteins; Viruses; Zika virus; Zika Virus - metabolism; Zika Virus Infection
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.202200351

The zika virus (ZIKV), transmitted to humans from the bites of Aedes Aegypti and Aedes Albopictus mosquitoes produces Zika fever and neurodegenerative disorders that despite affecting millions of people, most recently in Africa and the Americas, has been declared a neglected tropical disease by the World Health Organization. In this work, atomistic molecular dynamics simulations followed by rigorous analysis of the intermolecular interactions reveal crucial aspects of the initial virus⋯cell molecular recognition and attachment, events that trigger the infectious cycle. Previous experimental studies have shown that Dermatan Sulfate (DS) and Chondroitin Sulfate A (CSA), two glycosaminoglycans which are actually epimers to each other and that are structural constituents of receptors expressed in cell membranes, are the preferred anchorage sites, with a marked preference for DS. Our calculations rationalize this preference from a molecular perspective as follows: when free of the virus, DS has one sulfate group that does not participate in intramolecular strong hydrogen bonds, thus, it is readily available to interact with the envelope protein of the virus (Zika−E), then, after formation of the complexes, Zika−E⋯DS exhibits ten strong salt brides connecting the two fragments against only six salt bridges and two hydrogen bonds in Zika−E⋯CSA. Our results complement the current view of the interaction between the virus and the receptor glycosoaminoglycans revealing that the negatively charged carboxylate groups in CSA and DS are just as important as the sulfates because of the formation of equally strong salt bridges with the positively charged Arginine and Lysine aminoacids in the envelope protein of the virus. Ten strong salt bridges between the envelope protein and Dermatan Sulfate (DS) determine the marked preference for this GAG over Chondroitin Sulfate A (CSA) which only has six strong salt bridges and two charge assisted hydrogen bonds with the E protein in the initial molecular recognition and attachment of the Zika virus to cell receptors.