Structure prediction of gBP21 protein of L. donovani and its molecular interaction.

Visceral leishmaniasis (Kala-azar) is a fatal disease caused by the obligate intracellular parasite Leishmania donovani and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. RNA editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mRNAs are edited post-transcriptionally by the guide RNAs with the addition or deletion of uridine residues. The aim is to block the gBP21 protein involved in RNA editing process thereby other direct and indirect protein activity is reduced and ultimately the editing process in L. donovani is disturbed and it will inhibit the growth. RNA editing factors are RNA-linked proteins essential for in vivo editing i.e. mitochondrial RNA binding protein1 (MRP 1) originally called as gBP21. The model of L. donovani gBP21 (gBP21Ldv) showed that this protein bears an anti-parallel ß sheet (segregated α and ß regions) with ß-ß-ß-ß-α-ß-ß-ß-ß-α-type topology ("whirly" transcription-factor fold). Each of the four ß strands within a given ß-ß-ß-ß-α repeats and form a curved anti-parallel ß-sheet that packs perpendicularly against the sheet from the other repeat. Among all of the computationally screened compounds by the GLIDE program (Schrödinger) and GOLD program hyperoside1a, posaconazole, quercetin, and pentanediol, 427 exhibited higher binding affinities with the modeled gBP21 protein of L. donovani. Ligandfit program (DSv2.5) revealed that DNA, RNA polymerase inhibitors acyclovir, mitomycin C, and daunorubicin have better binding affinity towards gBP21Ldv. These compounds may be given in combination with miltefosine (first line therapy) against patients with VL and other associated disorders like anemia.