Dolutegravir Inhibition of Matrix Metalloproteinases Affects Mouse Neurodevelopment

• DOI: 10.1007/s12035-021-02508-5
• Publication Date: 2021-08-14T08:03:01Z
• Authors: Aditya N. Bade; JoEllyn M. McMillan; Yutong Liu; Benson J. Edagwa; Howard E. Gendelman
• Keywords: Dolutegravir

Dolutegravir (DTG) is a first-line antiretroviral drug (ARV) used in combination therapy for the treatment of human immunodeficiency virus type-1 (HIV-1) infection. The effective, safe, and well tolerated. Nonetheless, concerns have recently emerged its usage pregnant women or those child-bearing age. Notably, DTG-based ARV regimens been linked to birth defects seen as consequence periconceptional usages. To this end, uncovering an underlying mechanism DTG-associated adverse fetal development outcomes has gained clinical basic research interest. We now report that DTG inhibits matrix metalloproteinases (MMPs) activities could affect neurodevelopment. broad-spectrum MMPs inhibitor binds Zn++ at enzyme's catalytic domain. Studies performed mice show readily reaches central nervous system during gestation MMP activity. Postnatal screenings brain health pups identified neuroinflammation neuronal impairment. These abnormalities persist utero exposure. conclude inhibition potential prenatal postnatal