Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches

Sharma, Abhilasha; Vora, Jaykant; Patel, Dhaval; Sinha, Sonam; Jha, Prakash Chandra; Shrivastava, Neeta

doi:10.1080/07391102.2020.1846624

Cited by 44 publications

(53 citation statements)

References 74 publications

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“…The protein-ligand complexes showed a slight decrease in SASA values which indicated that in the protein-ligand complexes, the surface of the protein exposed to the aqueous solvent is reduced due to the ligand binding. Similarly, in a previous study on the remdesivir-protein system, a decrease in SASA values for protein-ligand complexes was observed [60]. The number of hydrogen bonds (H-bond) analysis indicates the strength and specificity of ligand for binding to the active site of protein as mentioned earlier [59].…”

Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 58%

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Nath

Goyal

2021

J Mol Model

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Structure and conformational behaviour of a putative β-1,4-glucosidase of glycoside hydrolase family 3 ( Ps GH3) from Pseudopedobacter saltans was predicted by using in-silico tools. Ps GH3 modeled structure constructed using Phyre2 displayed multidomain architecture comprising an N-terminal ( β / α ) 8 -fold domain followed by ( α / β ) 6 -sandwich domain, PA14 domain, and a C-terminal domain resembling an immunoglobulin fold. Ramachandran plot displayed 99.3% of amino acids in the allowed region and 0.7% residues in the disallowed region. Multiple sequence alignment (MSA) and structure superposition of Ps GH3 with other homologues from GH3 family revealed the conserved residues, Asp274 and Glu624 present in loops LA and LB, respectively originating from N-terminal domain act as catalytic residues. The volume and area calculated for Ps GH3 displayed a deep active-site conformation comparable with its homologues, β-1,4-glucosidases (GH3) of Kluyveromyces marxianus and Streptomyces venezuelae. Molecular dynamic (MD) simulation of Ps GH3 structure for 80 ns suggested stable and compact structure. Molecular docking studies revealed deeper active site conformation of Ps GH3 that could house larger cellooligosaccharides up to 7° of polymerization (DP7). The amino acid residues, Ala86, Leu88, Cys275, Pro483, Phe493, Asn417, Asn491, Pro492, and Leu495 created a binding pocket near the catalytic cleft, crucial for ligand binding. MD simulation of Ps GH3 in the presence of cellooligosaccharides, viz., cellobiose and celloheptaose showed stability in terms of RMSD, R g , and SASA values till 80 ns. The calculation of average number of hydrogen bond (H-bond), interaction energy, and binding free energy confirmed the stronger binding affinity of the larger cellooligosaccharides such as celloheptaose in the binding cavity of Ps GH3.

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Section: Molecular Dynamics Of Protein-ligand Complexessupporting

confidence: 58%

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Nath

Goyal

2021

J Mol Model

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“…51 The versatility of andrographolide as a SARS-CoV-2 antiviral is demonstrated by its potential to bind to several important targets at various stages of viral attachment, replication, and host-pathogen interactions. [29][30][31][32][33][34][36][37][38][39] This property may be an important advantage to any potential therapeutic agent being developed. Viral life cycle modeling studies have suggested that effective infection attenuation of repurposed drugs is more likely to be achieved when multiple segments of the viral life cycle are targeted, especially when timely administration of an antiviral in the early phases of infection is challenging in reallife settings.…”

Section: Discussion: Antiviral Evidence Against Sars-cov-2mentioning

confidence: 99%

“…59 Two papers predicted good binding of andrographolide and its derivatives with RdRp. 34,37 At present, the first and only antiviral currently approved by the U.S. FDA for the treatment of severe COVID-19, Remdesivir, is an antiviral that is thought to act through inhibition of RdRp, though its benefit in lowering mortality in COVID-19 patients remains to be investigated. 60 Remdesivir is a repurposed broad-spectrum antiviral against RNA viruses, originally developed for Ebola.…”

Section: Discussion: Antiviral Evidence Against Sars-cov-2mentioning

confidence: 99%

“…neoandrographolide and 14-deoxyandrographolide have stronger binding affinity than the parent compound andrographolide, and can potentially bind to and block the nucleotide entry site of RdRp. 34,37 Several in silico studies collectively indicated the potential of andrographolide binding to SARS-CoV-2 3CL pro , [30][31][32][34][35][36][37][38][39] supported by a target-based in vitro study. 38 3CL pro is an important protease enzyme involved in viral genome replication, transcription, translation, and other cellular processes in coronaviruses, 63,64 though details of its molecular processes in SARS-CoV-2 are yet to be fully elucidated.…”

Section: Discussion: Antiviral Evidence Against Sars-cov-2mentioning

confidence: 99%

“…However, andrographolide and related compounds were predicted to have binding affinity to several key components of the SARS-CoV-2 life cycle and pathogenicity. 29,[31][32][33][34][35][36][37][38][39] This potential ability to target multiple pathways of viral attachment, replication, and function may provide a unique advantage for andrographolide to be investigated as a versatile antiviral against SARS-CoV-2. When comparison is made between andrographolide and its analogs, the analogs, especially neoandrographolide and bisandrographolide, have better predicted binding affinities regardless of target receptor.…”

Section: Discussion: Antiviral Evidence Against Sars-cov-2mentioning

confidence: 99%

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Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

Lim

Chan

Tan

et al. 2021

Natural Product Communications

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Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

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Mulberroside F improves airway hyperresponsiveness and inflammation in asthmatic mice

Huang,

Wu,

Hsu

et al. 2023

The Kaohsiung J of Med Scie

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Mulberroside F is isolated from the leaves and roots of Morus alba L. Here, we investigated whether mulberroside F could alleviate airway inflammation and eosinophil infiltration in the lungs of asthmatic mice. We also examined whether mulberroside F attenuated inflammatory responses in human tracheal epithelial BEAS‐2B cells. Female BALB/c mice were sensitized and challenged with ovalbumin (OVA), and administered different doses of mulberroside F via intraperitoneal injection. Additionally, tumor necrosis factor (TNF)‐α‐stimulated BEAS‐2B cells were treated with various doses of mulberroside F, followed by detection of the expressions of inflammatory cytokines and chemokines. The results demonstrated that mulberroside F mitigated the levels of proinflammatory cytokines and chemokines, and CCL11, in inflammatory BEAS‐2B cells. Mulberroside F also suppressed reactive oxygen species (ROS) production and ICAM‐1 expression in TNF‐α‐stimulated BEAS‐2B cells, which effectively suppressed monocyte cell adherence. In an animal model of asthma, mulberroside F treatment attenuated airway hyperresponsiveness, eosinophil infiltration, and goblet cell hyperplasia. Mulberroside F treatment also decreased lung fibrosis and airway inflammation in OVA‐sensitized mice. Moreover, mulberroside F significantly reduced expressions of Th2‐associated cytokines (including interleukin(IL)‐4, IL‐5, and IL‐13) in bronchoalveolar lavage fluid compared to OVA‐sensitized mice. Our results confirmed that mulberroside F is a novel bioactive compound that can effectively reduce airway inflammation and eosinophil infiltration in asthmatic mice via inhibition of Th2‐cell activation.

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Identification of natural inhibitors against prime targets of SARS-CoV-2 using molecular docking, molecular dynamics simulation and MM-PBSA approaches

Cited by 44 publications

References 74 publications

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Structure and dynamics analysis of multi-domain putative β-1,4-glucosidase of family 3 glycoside hydrolase (PsGH3) from Pseudopedobacter saltans

Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

Mulberroside F improves airway hyperresponsiveness and inflammation in asthmatic mice

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