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Single Nucleotide Polymorphism Induces a Positive Selection Pressure at Gag-Pol Sites in Human Immunodeficiency Virus Favoring Drug Resistance Mutations

Single Nucleotide Polymorphism Induces a Positive Selection Pressure at Gag-Pol Sites in Human Immunodeficiency Virus Favoring Drug Resistance Mutations

Amreen Zahra1, Mushtaq A. Saleem1*, Hasnain Javed2, Muhammad Azmat Ullah Khan3, Muhammad Naveed1 and Abdul Rauf Shakoori4

1Department of Biochemistry and Biotechnology, University of Central Punjab, Lahore 54782, Pakistan
 2Advanced Diagnostic Laboratory, Punjab AIDS Control Programme, Government of Punjab, Lahore 54000, Pakistan
 3Department of Biochemistry and Molecular Biology, University of Gujrat, Gujrat 50700, Pakistan
 4School of Biological Sciences, University of the Punjab, Quaid-I-Azam Campus, Lahore 54590, Pakistan

*      Corresponding author: dr.mushtaq@ucp.edu.pk

 

ABSTRACT

Human immunodeficiency virus the retrovirus causes AIDS. HIV mainly targets the body’s immune system, including the CD4 cells, which help the immune system fight off infections. Gag-Pol are the principal viral elements in HIV-1, which cause disease initiation and progression. Here we present a comprehensive study, where both the in vitro and in-silico analyses were performed on HIV-1 from isolates of the Punjab area of Pakistan. The main objective in the current study was to study the hypervirulence of SNPs in the Gag-Pol proteins by molecular modeling approaches. Mutational analysis in our study revealed S61A, S61M, S61Y, S61G, S61Q and M90L as the most hypervirulent mutations. This induces a selection pressure and a rate of increased virulency on Gag-Pol cleavage sites. These results significantly highlight the fact that the identified SNPs possibly contribute towards a positive selection pressure contributing to the identification of novel mutations like S61A, S61M and M90L at Gag-Pol cleavage sites harboring dominant drug resistance mutations. 3D structure validation demonstrated 87.3% in Gag and 92.5% in Pol in the most favored regions. Dolutegravir, a protease inhibitor, was used for molecular docking to reveal the drug resistance sites among the isolates under investigation. However, strikingly the binding energies resulted were -7.9 kcal/mol for Pol and -5.7 kcal/mol in Gag that predicted that SNPs in the Pol gene could be one of the reasons for drug resistance and the primary site of mutations progressing the onset of infection. These computational strategies will thus help in performing large scale studies and also in the development of novel medicines for the cure of HIV-1.
 

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Pakistan Journal of Zoology

October

Vol. 53, Iss. 5, Pages 1603-2000

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