Design and identification of novel annomontine analogues against SARS-CoV-2: An in-silico approach

Abstract

Aims: COVID-19 has currently emerged as the major global pandemic affecting the lives of people across the globe. It broke out from Wuhan Province of China, first reported to WHO on 31 st December 2019 as "Pneumonia of unknown cause". Over time more people were infected with this virus, and the only tactic to ensure safety was to take precautionary measures due to the lack of any effective treatment or vaccines. As a result of unavailability of desired efficacy for previously repurposed drugs, exploring novel scaffolds against the virus has become the need of the hour. Main methods: In the present study, 23 new annomontine analogues were designed representing β-Carboline based scaffolds. A hypothesis on its role as an effective ligand was laid for target-specific binding in SARS-CoV-2. These molecules were used for molecular docking analysis against the multiple possible drug targets using the Maestro Interface. To ensure the drug safety of these molecules ADME/Tox analysis was also performed. Key findings: The molecular docking analysis of the 23 novel molecules indicated the efficiency of these derivates against COVID-19. The efficiency of molecules was computed by the summation of the docking score against each target defined as Lig E Score and compared against Hydroxycholoquine as a standard. Based on the docking score, the majority of the annomontine derivatives were found to have increased binding affinity with targets as compared to hydroxycholoquine. Significance: Due to the lack of efficiency, effectiveness, and failure of already repurposed drugs against the COVID-19, the exploration of the novel scaffold that can act as effective treatment is much needed. The current study hence emphasizes the potential of Annomontine based -β-Carboline derivatives as a potential drug candidate against COVID-19.

Virtual and In Vitro Screening of Natural Products Identifies Indole and Benzene Derivatives as Inhibitors of SARS-CoV-2 Main Protease (Mpro)

“…More than 23 annomontine analogs, which represent a special class of β-carboline, were designed and docked against multiple SARS-CoV-2. Based on docking scores, the binding affinities of these annomontine derivatives were better compared to hydroxycholoquine [ 57 ]. While the potential of different β-carbolines in binding to several SARS-CoV-2 proteins has been demonstrated computationally, our results are the first to show direct in vitro experimental evidence against SARS-CoV-2 M pro .…”

Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities

“…N -heterocyclic compounds have become progressively in demand for their exclusive structural identity exhibiting myriad medicinal and pharmaceutical activities [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. The saturated and unsaturated N -heterocyclic analogues have exceptionally interesting architecture for drug design and development [ 7 , 17 , 18 , 19 , 20 , 21 ].…”

Role of Phytochemicals and their Derivatives in Targeting Stem Cell Markers in Breast and Cervical Cancer

“…Because CSCs are difficult to identify, there is a need to identify stem cell markers. In this study, we selected the two most common types of gynecological cancers affecting women worldwide; breast cancer, and cervical cancer to analyze the stem cell markers, and target the most significant stem cell marker by novel plant-based metabolites and their derivatives like hydroxyl-piperloungumines, Coumaperine, annomontine, curcumin derivatives and 6,6'-Dihydroxythiobinupharidine (DTBN) [6][7][8][9][10] .…”