Dolutegravir Inhibition of Matrix Metalloproteinases Affects Mouse Neurodevelopment.

ABSTRACT: 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 drug is effective, safe, and well tolerated. Nonetheless, concerns have recently emerged for its usage in pregnant women or those of child-bearing age. Notably, DTG-based ARV regimens have been linked to birth defects seen as a consequence of periconceptional usages. To this end, uncovering an underlying mechanism for DTG-associated adverse fetal development outcomes has gained clinical and basic research interest. We now report that DTG inhibits matrix metalloproteinases (MMPs) activities that could affect fetal neurodevelopment. DTG is a broad-spectrum MMPs inhibitor and binds to Zn⁺⁺ at the enzyme's catalytic

SUBMITTER: Bade AN 

PROVIDER: S-EPMC8599359 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature