Identification of novel inhibitory candidates against two major Flavivirus pathogens via CADD protocols: in silico analysis of phytochemical binding, reactivity, and pharmacokinetics against NS5 from ZIKV and DENV

Rasool, Nouman; Majeed, Arshia; Riaz, Fareeha; Hussain, Waqar

doi:10.1007/s11224-020-01577-x

Cited by 7 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 2750 naturally occurring compounds were first inspected for their drug-likeness properties. ADMET analysis is primarily carried out to identify the potentials of these compounds to be used as a human drug in future during clinical experiments [18,23,26,[40][41][42][43][44]. Out of 2750 compounds, 1689 were selected based on Lipinski's rule of five.…”

Section: Resultsmentioning

confidence: 99%

“…But as in our case, no previously reported and biologically validated known inhibitors were present, and a threshold of -8.5 kcal/mol was chosen so that we do not have to further assess all compounds and a reasonable number of compounds can be selected. A similar approach has been opted in various previously reported studies [18,23,26,40,41,44].…”

Section: Molecular Docking Screening Resultsmentioning

confidence: 99%

“…According to the results shown in Table 2, the RMSD values were observed to have substantial changes while looking in complexes of HR1 with other phytochemicals; however, within these five complexes, these values were very 14 BioMed Research International low, i.e., less than 3 Å [18,44]. Furthermore, the graphs shown in Figure 2 depicted fewer fluctuations in the radius of gyration.…”

Section: Simulation Analysismentioning

confidence: 99%

See 2 more Smart Citations

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies

Majeed

Hussain

Yasmin

et al. 2021

BioMed Research International

Self Cite

View full text Add to dashboard Cite

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Screening Resultsmentioning

confidence: 99%

Section: Simulation Analysismentioning

confidence: 99%

See 1 more Smart Citation

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies

Majeed

Hussain

Yasmin

et al. 2021

BioMed Research International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, 29 compounds inhibited the ZIKV-NS5 protein in the RNA-dependent RNA polymerase (RdRp) domain, the highest affinity energy being found for the flavonoid isopomiferin (−9.2 kcal/mol). This compound was also identified as a potential inhibitor of both NS5 MTase and NS5 RdRp of ZIKV in addition to four dengue serotypes proteins [ 47 ]. Moreover, polydatin, dihydrogenistin, liquiritin, rhapontin, and cichoriin were successfully bound inside the pocket of ZIKV NS5 RdRp [ 48 ].…”

Section: Nps With Potential Anti-zikv Activitymentioning

confidence: 99%

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Pereira

Santos

Campana

et al. 2023

Viruses

View full text Add to dashboard Cite

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present anti-ZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI ≥ 25,000) and anisomycin (SI ≥ 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI ≥ 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

show abstract

“…Cannflavin A exhibited remarkable binding affinity values against the protein NS5 protein (NS5 MTase and NS5 RdRp) of Zika virus in addition to four serotypes of the dengue virus. 63 Cannflavin A is also among the phytochemicals that are predicted to show efficient docking to the helicase (RNA site), helicase (ATP site), methyltransferase, and RNA-dependent RNA polymerase of Zika virus with binding energies of −131.7, −134.6, −126.9, and −120.3 kJ/mol, respectively. 64 …”

Section: Biological Activities Of Cannflavinsmentioning

confidence: 99%

Chemistry and Biological Activities of Cannflavins of the Cannabis Plant

Abdel-Kader,

Radwan,

Metwaly

et al. 2023

Cannabis and Cannabinoid Research

View full text Add to dashboard Cite

Background: Throughout history, Cannabis has had a significant influence on human life as one of the earliest plants cultivated by humans. The plant was a source of fibers used by the oldest known civilizations. Cannabis was also used medicinally in China, India, and ancient Egypt. Delta-9-tetrahydrocannabinol (Δ 9 -THC), the main psychoactive compound in the plant was identified in 1964 followed by more than 125 cannabinoids. More than 30 flavonoids were isolated from the plant including the characteristic flavonoids called cannflavins, which are prenylated or geranylated flavones. Material and Methods: In this review, the methods of extraction, isolation, identification, biosynthesis, chemical synthesis, analysis and pharmacological activity of these flavonoids are described. Results: The biosynthetic routes of the cannflavins from phenylalanine and malonyl CoA as well as the microbial biotransformation are also discussed. Details of the chemical synthesis are illustrated as an alternative to the isolation from the plant materials along with other possible sources of obtaining cannflavins. Detailed methods discussing the analysis of flavonoids in cannabis are presented, including the techniques used for separation and detection. Finally, the various biological activities of cannflavins are reviewed along with the available molecular docking studies. Conclusion: Despite the low level of cannflavins in cannabis hamper their development as naturally derived products, efforts need to be put in place to develop high yield synthetic or biosynthetic protocols for their production in order for their development as pharmaceutical products.

show abstract

Identification of novel inhibitory candidates against two major Flavivirus pathogens via CADD protocols: in silico analysis of phytochemical binding, reactivity, and pharmacokinetics against NS5 from ZIKV and DENV

Cited by 7 publications

References 50 publications

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies

Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Chemistry and Biological Activities of Cannflavins of the Cannabis Plant

Contact Info

Product

Resources

About