Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations
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Date
2021Author
Mikas, Sello Given
Isaacs, Darren
Chitongo, Rumbidzai
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The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light
to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG
containing regimens have shown a high genetic barrier against HIV-1 isolates carrying specific resistance mutations
when compared with other class of regimens.We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistanceassociated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences
(n = 20) and (n = 287) sequences data derived from HIV Los Alamos National Laboratory database. The possible
impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a
3D model of the HIV-1 IN complex and interaction analysis was performed using PyMol to validate DTG binding to
the Wild type and seven mutant structures.