Infection Dynamics of ATG8 in Leishmania: Balancing Autophagy for Therapeutics.

Vrushali Guhe, Farah Anjum, Alaa Shafie, Md Imtaiyaz Hassan, Visweswara Rao Pasupuleti, Shailza Singh

Molecules (Basel, Switzerland) 2022 May 13

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In many regions of the world, Leishmaniasis is a cause of substantial mortality and ailment. Due to impediment in available treatment, development of novel and effective treatments is indispensable. Significance of autophagy has been accentuated in infectious disease as well as in Leishmaniasis, and it is having capability to be manifested as a therapeutic target. By evincing autophagy as a novel therapeutic regime, this study emphasized on the critical role of ATG4.1-ATG8 and ATG5-ATG12 complexes in Leishmania species. The objective here was to identify ATG8 as a potential therapeutic target in Leishmania. R71T, P56E, R18P are the significant mutations which shows detrimental effect on ATG8 while Arg276, Arg73, Cys75 of ATG4.1 and Val88, Pro89, Glu116, Asn117, and Gly120 are interacting residues of ATG8. Along with this, we also bring into spotlight an enticing role of Thiabendazole derivatives that interferes with the survival mechanisms by targeting ATG8. Further, the study claims that thiabendazole can be a potential drug candidate to target autophagy process in the infectious disease Leishmaniasis.

Citation

Vrushali Guhe, Farah Anjum, Alaa Shafie, Md Imtaiyaz Hassan, Visweswara Rao Pasupuleti, Shailza Singh. Infection Dynamics of ATG8 in Leishmania: Balancing Autophagy for Therapeutics. Molecules (Basel, Switzerland). 2022 May 13;27(10)