A Mechanism of Action for Hydroxychloroquine and Azithromycin to Inhibit Coronavirus Disease COVID-19

Hydroxychloroquine and azithromycin have clinical promise to treat COVID-19, although its mechanism of action to inhibit the replication of coronavirus is unclear. Using molecular modeling and recent discoveries made by this lab on the structure of nucleic acids, a mechanism of action is developed for hydroxychloroquine (HCQ) and azithromycin (AZR) to inhibit the replication of the coronavirus disease COVID-19. The mechanism involves: (1) binding the Cl end-element of HCQ through ionic means to adjacent phosphate groups of the uracil nucleotide; (2) forming an intermolecular hydrogen bond of an NH group of HCQ to an open oxygen element of uracil; (3) binding OH end group of HCQ through ionic means with adjacent phosphate groups of the adenine nucleotide. The mechanism of action is extended to AZR as a drug delivery vector that collects HCQ and two ions of positive two charge, such as Mg2+, Zn2+ or Ca2+, and delivers the assembly to a secondary structure of single-strand RNA. As with HCQ, the structural biology of AZR is compatible for use as a collection and delivery vesicle including: (1) open access for the Cl end element and the NH group of HCQ to align and bind with Uracil, and (2) the ability to deliver and bind through ionic coupling of the OH end group of HCQ to the adenine nucleotide. The molecular ionic attachment of HCQ to RNA nucleotides enabled by AZR results in the inhibition of the replication capability of the coronavirus disease COVID-19.