Evaluation of Annona muricata Acetogenins as Potential Anti-SARS-CoV-2 Agents Through Computational Approaches.

Kingsley Chukwuemeka Patrick-Iwuanyanwu,Shashanka K Prasad,Sushma Pradeep,Norma Flores-Holguín,Daniel Glossman-Mitnik,Chukwuebuka Egbuna,Chandan Shimavallu,Juan Frau,Joaquín Ortega Castro,Shiva Prasad Kollur,Najat Marraiki,Olga Kosakowska,William C Cho,Mihnea-Alexandru Gaman,Asad Syed

doi:10.3389/fchem.2020.624716

Abstract

Annona muricata, a tropical plant which has been extensively used in ethnomedicine to treat a wide range of diseases, from malaria to cancer. Interestingly, this plant has been reported to demonstrate significant antiviral properties against the human immunodeficiency virus, herpes simplex virus, human papilloma virus, hepatitis C virus and dengue virus. Additionally, the bioactive compounds responsible for antiviral efficacy have also shown to be selectively cytotoxic while inhibiting tumorigenic cell growth without affecting the normal cell growth. Annonaceous Acetogenins are a class of bioactive compounds exclusive to the Annonaceae family at which the plant A. muricata belongs. In the current study, we have created a library of Acetogenins unique to the plant, comprising of Annomuricin A, Annomuricin B, Annomuricin C, Muricatocin C, Muricatacin, cis-Annonacin, Annonacin-10-one, cis-Goniothalamicin, Arianacin and Javoricin, for in silico and theoretical evaluations against the SARS-CoV-2 spike protein in an attempt toward promotion of plant based drug development for the current pandemic of coronavirus disease 2019 (COVID-19). We found that all the Acetogenins showing in silico spike protein significantly docking with good binding affinities. Moreover, we envision A. muricata Acetogenins can be further studied by in vitro and in vivo models to identify potential anti-SARS-CoV-2 agents.

Highlights

Annona muricata (L.), commonly called Soursop (English) or Lakshmanaphala (Kannada), is a tropical plant known for its wide range of applications in ethnomedicinal practices (Moghadamtousi et al, 2015; Gavamukulya et al, 2017; Prasad et al, 2019)
Ten Acetogenins unique to A. muricata have been evaluated for the SARS-CoV-2 inhibition potential, by means of targeting the spike protein
The crystal structure of SARS-CoV-2 spike receptor-binding domain bound with angiotensin converting enzyme 2 (ACE2) (PDB ID- 6M0J) (Supplementary Figure S1) was considered and downloaded from the biological structural database of proteins, i.e. Protein Data Bank (PDB)

Summary

Introduction

Annona muricata (L.), commonly called Soursop (English) or Lakshmanaphala (Kannada), is a tropical plant known for its wide range of applications in ethnomedicinal practices (Moghadamtousi et al, 2015; Gavamukulya et al, 2017; Prasad et al, 2019). Found exclusive to the Annonaceae family, the annonaceous Acetogenins are one class of phytochemicals that have been investigated thoroughly for their potent biomedical properties. The above observations confirm the broad-spectrum antiviral activity of A. muricata phytochemicals, which may be responsible for the other biomedical properties. In this first combination of theoretical and computational studies on annonaceous Acetogenins, we have created a library of Annomuricin A, Annomuricin B, Annomuricin C, Muricatocin C, Muricatacin, cis-Annonacin, Annonacin-10-one, cis-Goniothalamicin, Arianacin and Javoricin, to investigate their in silico antiSARS-CoV-2 activity. This study provides evidence for drug development exercises toward mitigation of the current pandemic, coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus

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Conclusion