Abstract

Sabahat Yasmeen Sheikh¹, Waseem Ahmad Ansari² Firoj Hassan¹, Mohammad Faheem Khan², , Syed Shah Mohammed Faiyaz⁴, Yusuf Akhter³, Abdul Rahman Khan¹ and Malik Nasibullah^1*

DOI : http://dx.doi.org/10.13005/ojc/390101

Due to the lack of approved vaccines against Cutaneous Leishmaniasis (CL), chemotherapy is the only treatment option. Presently, none of the current CL drugs have high levels of efficacy and safety profiles. Thus, the development of new and safer drugs is urgently needed. Drug repurposing can be used for the development of new therapeutic activities. Phosphomannomutase (PMM) has become highlighted as a potential drug target due to its important role in the biosynthesis of glycoconjugates which is essential for parasite virulence. To identify new promising lead molecules, we have performed virtual screening of 8,500 drugs and selected 46 drugs for docking simulation through the Glide module of Schrodinger software. The saquinavir and grazoprevir showed the highest binding affinity (-10.144 and -10.131 kcal/mole). To find the stability of both complexes, molecular dynamics (MD) simulation were performed at 100ns. The grazoprevir-2i54 and saquinavir-2i54 complexes showed good stability in the active site of the receptor. It could be an alternative drug for the treatment of CL.

Amphotericin B; Drug Repurposing; Molecular Docking Simulation; Molecular Dynamics Simulation; Miltefosine; Phosphomannomutase

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