Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

Sarwar, Muhammad Waseem; Riaz, Adeel; Dilshad, Syed Muhammad Raihan; Al‐Qahtani, Ahmed; Nawaz-ul-Rehman, Muhammad Shah; Mubin, Muhammad

doi:10.1186/s12900-018-0084-5

Cited by 43 publications

(35 citation statements)

References 26 publications

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“…Flavones are dual fused aromatic rings (A and C) with an extension of a benzene ring (B) at position 2 of ring C (Figure 3) [87]. The skeleton "ring A fused with ring C" has previously reported to possess antiviral activity against the dengue virus NS2B-NS3 complex [88]. Moreover, hydroxylation on ring A, particularly on positions 5 and 7, was found to be favorable for antiviral activity against the influenza A virus [89].…”

Section: Structure-activity Relationship Among Potential Antiviral Flmentioning

confidence: 99%

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

159

101

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Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.

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Section: Structure-activity Relationship Among Potential Antiviral Flmentioning

confidence: 99%

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

159

101

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“…The present study emphasizes on the modeling of receptor binding domain (RBD) of nCoV-SP and generating a stable protein model which puts insight into its structure for possible interaction study of the protein with our choice of inhibitors and binds to the possible important residues of RBD that are crucial in interaction with the human receptor and further viral entry into the cell and pathogenesis. Flavonoids with its broad biological activity including antiviral activity against other viruses as well as SARS [33][34][35][36][37][38][39][40][41][42][43][44] were taken under consideration in this study, as molecular works of flavonoids against SARS-CoV and SARS-CoV-2 have not been done yet.…”

Section: Discussionmentioning

confidence: 99%

“…Different flavonoids with antioxidant, hepatoprotective, antibacterial, anti-inflammatory, anticancer and antiviral properties from different literatures were considered [15][16]. Flavonoids possessing antiviral activity against some viruses including coronavirus were also taken into consideration [33][34][35][36][37][38][39][40][41][42][43][44]. However, no study on the molecular level of flavonoids has been reported against nCoV-SP and, hence, flavonoids were considered in this computational study against For better reliability and precise results two docking software, PyRx [45] and iGEMDOCK [46] (N=800), 80 generation and 10 solutions were carried out with our choice of ligands in iGEMDOCK against both the protein models [47,48].…”

Section: Ligand Selection and Ligand File Preparationmentioning

confidence: 99%

Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis

Bhowmik¹,

Nandi²,

Kumar

2020

Preprint

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In this study we aimed at the receipt binding domain of S protein and ACE-2 receptor as a promising drug targets against SARS-CoV-2. Flavonoids with anti-viral properties were taken as ligand for molecular docking. Selected flavonoids showed extremely good pharmacokinetics properties with good absorption, solubility, metabolism, excretion,distribution, bioavailability and minimal toxicity. These identified lead flavonoids may act as potential compound for the development of effective drugs and may help in controlling the rapid spread of SARS-CoV-2 by potentially inhibiting the virus entry into the host cell.

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“…Hence, to overcome such situation presently, available more resources, much faster, and advance scientific techniques need to be adopted and explored. Earlier, a number of studies have proposed various traditional and specific methods for the identification of different chemical entities and demonstrated their selective inhibition mechanism and inhibitory efficacy against NS3‐NS2B protease complex at different levels …”

Section: Introductionmentioning

confidence: 99%

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

Bhowmick

Alissa

Wabaidur

et al. 2020

J of Molecular Recognition

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Dengue infection is the most common arthropod-borne disease caused by dengue viruses, predominantly affecting millions of human beings annually. To find out promising chemical entities for therapeutic application in Dengue, in the current research, a multi-step virtual screening effort was conceived to screen out the entire "screening library" of the Asinex database. Initially, through "Lipinski rule of five" filtration criterion almost 0.6 million compounds were collected and docked with NS3-NS2B protein. Thereby, the chemical space was reduced to about 3500 compounds through the analysis of binding affinity obtained from molecular docking study in AutoDock Vina. Further, the "Virtual Screening Workflow" (VSW) utility of Schrödinger suite was used, which follows a stepwise multiple docking programs such as -high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking, and in postprocessing analysis the MM-GBSA based free binding energy calculation. Finally, five potent molecules were proposed as potential inhibitors for the dengue NS3-NS2B protein based on the investigation of molecular interactions map and protein-ligand fingerprint analyses. Different pharmacokinetics and drug-likeness parameters were also checked, which favour the potentiality of selected molecules for being drug-like candidates. The molecular dynamics (MD) simulation analyses of protein-ligand complexes were explained that NS3-NS2B bound with proposed molecules quite stable in dynamic states as observed from the root means square deviation (RMSD) and root means square fluctuation (RMSF) parameters. The binding free energy was calculated using MM-GBSA method from the MD simulation trajectories revealed that all proposed molecules possess such a strong binding affinity towards the dengue NS3-NS2B protein. Therefore, proposed molecules may be potential chemical components for effective inhibition of dengue NS3-NS2B protein subjected to experimental validation.

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Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease

Cited by 43 publications

References 26 publications

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Evaluation of Flavonoids as 2019-nCoV Cell Entry Inhibitor Through Molecular Docking and Pharmacological Analysis

Structure‐guided screening of chemical database to identify NS3‐NS2B inhibitors for effective therapeutic application in dengue infection

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