In silico investigation of binding propensity of hematoxylin derivative and damnacanthal for their potential inhibitory effect on HIV-1 Vpr from different subtypes

HIV-1, the causative agent of AIDS leads to many deaths worldwide though few options are available as therapeutics. To deal with the continuous mutation in the virus genome, requirement of new drugs is always there. Subtype variation plays a crucial role in case of HIV-1 therapeutics development. In this study, we want to investigate some pre examined molecules that can be effective for HIV-1 VPR. Inhibition of several protein-protein interactions with the small molecules will lead to identify some molecules as therapeutics other than the conventional drugs. We retrieved the sequences of different subtypes from the database and representative sequences were identified. Representative structures were modelled and validated using MD simulations. Forty molecules, showing anti Vpr activity in vitro were identified from literature survey and those were docked with each subtype representative structures. Two molecules a stable Hematoxylin Derivative (SHD) and Damnacanthal (D3), these were shown to be bind more effectively for all the subtypes. The stability of the protein and those two small molecule complexes were identified again with MD simulation followed by the binding energy calculation. Thus, these molecules can be thought as any option other than the conventional drug targeting HIV-1 Vpr.Communicated by Ramaswamy H. Sarma

Automated summary

HIV-1 virus, the causative agent of AIDS, leads to numerous deaths worldwide and lacks effective therapeutic options due to its continuous mutation. In this study, researchers investigated the efficacy of two small molecules, SHD and D3, in inhibiting HIV-1 Vpr. Through experiments and simulations, they confirmed the stability of the protein and the ability of these molecules to bind effectively.