Virtual Screening of candidate Bio-actives from selected medicinal plants against rilpivirine resistance in HIV

Abstract

HIV, the causative virus of AIDS, has posed a severe threat to global health for an extensiveperiod. Recent statistics show the magnitude of this challenge, with approximately 2.4 million people inIndia living with HIV, along with 41.97 thousand deaths which were reported in 2021. In the face of thisongoing crisis, patients have relied heavily on anti-retroviral therapies, among which Rilpivirine standsout as a key treatment option, particularly for individuals exhibiting low viral loads. However, the efficacyof Rilpivirine diminishes significantly in patientsagainst high viral loads of HIV-1C, leading to theemergence of drug-resistant strains. Consequently, there exists an urgent need to identify and developmore potent therapeutic agents to combat HIV infection. To address this, we performed an in-silicoinvestigation, utilizing virtual screening tools to explore potential alternative drugs to Rilpivirine for HIVtreatment.Our methodology involved mining data from reputable sources such as the PubChemand Zincdatabases to identify compounds with potential antiretroviral activity. We subjected these compounds toscreening using the SwissADME tool, evaluating their pharmacokinetic characteristics and adherence toLipinski's rule of five. Compounds demonstrating favourable properties, as indicated by zero violations inOSIRIS Property Explorer, were then prioritized for further analysis. The structural frameworks ofRilpivirine protein-ligand complexes, both native (7Z2D) and mutant (7Z2E) variants, were procured fromthe Protein Data Bank (PDB). Further, ligand molecules' structural configurations were sourced fromdatabases such as PubChem and Corinasoftware. Employing molecular docking simulations facilitated byHDOCK docking software, the binding affinities of these ligands against the receptor protein-ligandcomplexes were studied, from which, Schumannificine emerged as the most promising candidate,exhibiting the most stable binding interactions.In summation, out of 65 phytochemicals, ourcomprehensive investigation underscores the potential of Schumannificine (CID: 184890), an alkaloidcompound derived from the Schumanniophytonmagnificum plant as a novel and viable therapeutic optionfor HIV patients.These findings hold significant implications for advancing the development of moreefficacious treatments for HIV/AIDS and warrant further experimental validation and clinicalexploration.In silico study has proven to increase the ease of drug discovery, and in vitro and in vivostudies can be further done to completely verify this drug candidature.