Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis. Issue 20 (29th November 2022)

• Record Type: Journal Article
• Authors: Trivedi, Anchal; Ahmad, Rumana; Siddiqui, Sahabjada; Misra, Aparna; Khan, Mohsin Ali; Srivastava, Aditi; Ahamad, Tanveer; Khan, Mohd. Faheem; Siddiqi, Zeba; Afrin, Gazala; Gupta, Anamika; Upadhyay, Shivbrat; Husain, Ishrat; Ahmad, Bilal; Mehrotra, Sudhir; Kant, Surya
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 20(2022)
• Page Start: 9648
• Page End: 9700
• Publication Date: 2022-11-29
• Subjects: Immunoboosting agents -- spike glycoprotein -- ACE2 -- coronaviruses -- Ayurveda -- COVID-19; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1932601
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz . SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo . Graphical Abstract: UF0001 Communicated by Ramaswamy H. Sarma