Designing potential siRNA molecules for silencing the gene of the nucleocapsid protein of Nipah virus: A computational investigation

Mahfuz, A M U B; Khan, Md. Arif; Sajib, Emran Hossain; Deb, Anamika; Mahmud, Shafi; Hasan, Mahmudul; Saha, Otun; Islam, Ariful; Rahaman, Md. Mizanur

doi:10.1016/j.meegid.2022.105310

Cited by 8 publications

(12 citation statements)

References 65 publications

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“…To investigate protein–ligand complexes in a physiological setting and evaluation of the conformational flexibility and stability of protein systems, MD modeling is an important tool 54 , 55 . For all of the ligand-receptor complexes, our MD simulations revealed stable RMSD profiles and had more binding affinity, which shed light on the structural integrity of the docked complexes.…”

Section: Discussionmentioning

confidence: 99%

“…For all of the ligand-receptor complexes, our MD simulations revealed stable RMSD profiles and had more binding affinity, which shed light on the structural integrity of the docked complexes. Rg profiles are used to describe protein folding and degree of compactness, and all of the complexes had tolerable variations in their matching Rg profiles 55 . Computing comparative data, including RMSD, RMSF, SASA, and Rg, were performed through analyzing the MD trajectories to calculate the change in the distance between the specified ligand/protein atoms over the whole simulation period.…”

Section: Discussionmentioning

confidence: 99%

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Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae

Khan

Mahfuz

et al. 2022

Sci Rep

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Magnaporthe oryzae is one of the most notorious fungal pathogens that causes blast disease in cereals, and results in enormous loss of grain production. Many chemical fungicides are being used to control the pathogen but none of them are fully effective in controlling blast disease. Therefore, there is a demand for the discovery of a new natural biofungicide to manage the blast disease efficiently. A large number of new natural products showed inhibitory activities against M. oryzae in vitro. To find out effective biofungicides, we performed in silico molecular docking analysis of some of the potent natural compounds targeting four enzymes namely, scytalone dehydratase, SDH1 (PDB ID:1STD), trihydroxynaphthalene reductase, 3HNR (PDB ID:1YBV), trehalose-6-phosphate synthase, Tps1 (PDB ID:6JBI) and isocitrate lyase, ICL1 (PDB ID:5E9G) of M. oryzae fungus that regulate melanin biosynthesis and/or appresorium formation. Thirty-nine natural compounds that were previously reported to inhibit the growth of M. oryzae were subjected to rigid and flexible molecular docking against aforementioned enzymes followed by molecular dynamic simulation. The results of virtual screening showed that out of 39, eight compounds showed good binding energy with any one of the target enzymes as compared to reference commercial fungicides, azoxystrobin and strobilurin. Among the compounds, camptothecin, GKK1032A2 and chaetoviridin-A bind with more than one target enzymes of M. oryzae. All of the compounds except tricyclazole showed good bioactivity score. Taken together, our results suggest that all of the eight compounds have the potential to develop new fungicides, and remarkably, camptothecin, GKK1032A2 and chaetoviridin-A could act as multi-site mode of action fungicides against the blast fungus M. oryzae.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae

Khan

Mahfuz

et al. 2022

Sci Rep

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“…It is worth noting that small interfering RNAs (siRNAs) have the potential to play a crucial role in preventing the expression of disease-causing viral genes through the hybridization and subsequent inactivation of disease-causing viral mRNAs target complementarities via RNA interference (RNAi) [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Anticipating the Next Chess Move: Blocking SARS-CoV-2 Replication and Simultaneously Disarming Viral Escape Mechanisms

Casseb

Khayat²,

Souza³

et al. 2022

Genes

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The COVID-19 pandemic initiated a race to determine the best measures to control the disease and to save as many people as possible. Efforts to implement social distancing, the use of masks, and massive vaccination programs turned out to be essential in reducing the devastating effects of the pandemic. Nevertheless, the high mutation rates of SARS-CoV-2 challenge the vaccination strategy and maintain the threat of new outbreaks due to the risk of infection surges and even lethal variations able to resist the effects of vaccines and upset the balance. Most of the new therapies tested against SARS-CoV-2 came from already available formulations developed to treat other diseases, so they were not specifically developed for SARS-CoV-2. In parallel, the knowledge produced regarding the molecular mechanisms involved in this disease was vast due to massive efforts worldwide. Taking advantage of such a vast molecular understanding of virus genomes and disease mechanisms, a targeted molecular therapy based on siRNA specifically developed to reach exclusive SARS-CoV-2 genomic sequences was tested in a non-transformed human cell model. Since coronavirus can escape from siRNA by producing siRNA inhibitors, a complex strategy to simultaneously strike both the viral infectious mechanism and the capability of evading siRNA therapy was developed. The combined administration of the chosen produced siRNA proved to be highly effective in successfully reducing viral load and keeping virus replication under control, even after many days of treatment, unlike the combinations of siRNAs lacking this anti-anti-siRNA capability. Additionally, the developed therapy did not harm the normal cells, which was demonstrated because, instead of testing the siRNA in nonhuman cells or in transformed human cells, a non-transformed human thyroid cell was specifically chosen for the experiment. The proposed siRNA combination could reduce the viral load and allow the cellular recovery, presenting a potential innovation for consideration as an additional strategy to counter or cope COVID-19.

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“…Prior to optimizing and orienting their hydrogen-bond network, the docked complexes were first cleaned. Utilizing the TIP3P solvation model, a cubic cell of the simulation with periodic boundary conditions was generated [ 37 ]. In every direction the simulated cell was expanded by 20 Å from the docked complexes.…”

Section: Methodsmentioning

confidence: 99%

“…The Berendsen thermostat, together with constant temperature and pressure were used in the simulations for 100 ns (ns). Through the investigation of the simulation trajectory data, the root-mean-square deviation (RMSD), root-mean-square-fluctuation (RMSF), radius of gyration (Rg), hydrogen bond, and solvent-accessible surface area (SASA) were assessed [ 24 , 37 ].…”

Section: Methodsmentioning

confidence: 99%

In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaporthe oryzae

Khan¹,

Ahsan²,

Khan³

et al. 2023

Heliyon

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Designing potential siRNA molecules for silencing the gene of the nucleocapsid protein of Nipah virus: A computational investigation

Cited by 8 publications

References 65 publications

Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae

Highly potent natural fungicides identified in silico against the cereal killer fungus Magnaporthe oryzae

Anticipating the Next Chess Move: Blocking SARS-CoV-2 Replication and Simultaneously Disarming Viral Escape Mechanisms

In-silico prediction of highly promising natural fungicides against the destructive blast fungus Magnaporthe oryzae

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