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1.
Planta ; 258(6): 104, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878120

RESUMO

MAIN CONCLUSION: Simultaneous application of two sustainability approaches such as the application of biofertilizers to GM plants and microbe bioengineering to enhance physiological response and beneficial interaction with GM plants may have a significant impact on strengthening global food security amid climate change and the pandemic. The second sustainable development goal (SDG 02, Zero Hunger) aims global agricultural sustainability and food security challenges. The agriculture sector has been an integral part of developing countries for millions of farmers and their families. Their contribution provides stability of raw matter related to food availability. But climate change, higher population growth and worldwide pandemics are the main obstacles to food quality, higher crop productivity and global food security. Scientists are concerned with the manifestation of agriculture sustainability in the modern crop management approach to resolving the issues. It is the only way to higher yield productivity by protecting the environment, conserving natural resources, and slowing climate change. Several strategies can be an option to implement, yet the proposed two sustainability approach or 2S approach will be the significant way toward the goal of zero hunger. The first sustainability approach is an application of genetically modified (S1: GMO) Plants and the other is an application of beneficiary plant growth-promoting microbes (S2: Biofertilizers) to the plants for both higher crops and maintenance of the environment. This study summarizes the essential points of S1 and S2 for the widespread utilization of the 2S approach in agriculture and recommends the potential alternatives to be implemented to produce food for all. Simultaneous application of the 2S approach can defeat all threats to gain sustainability in agriculture.


Assuntos
Mudança Climática , Pandemias , Humanos , Agricultura , Produção Agrícola , Produtos Agrícolas
2.
J Biomol Struct Dyn ; 40(4): 1639-1658, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33047658

RESUMO

In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys-His catalytic dyad, and ligands that interact with the Cys145 assumed to be an effective approach to inhibit the Mpro. In this study, approximately 1400 cysteine-focused ligands were screened to identify the best candidates that can act as potent inhibitors against Mpro. Our results show that the selected ligands strongly interact with the key Cys145 and His41 residues. Covalent docking was performed for the selected candidates containing the acrylonitrile group, which can form a covalent bond with Cys145. All atoms molecular dynamics (MD) simulation was performed on the selected four inhibitors including L1, L2, L3 and L4 to validate the docking interactions. Our results were also compared with a control ligand, α-ketoamide (11r). Principal component analysis on structural and energy data obtained from the MD trajectories shows that L1, L3, L4 and α-ketoamide (11r) have structural similarity with the apo-form of the Mpro. Quantitative structure-activity relationship method was employed for pattern recognition of the best ligands, which discloses that ligands containing acrylonitrile and amide warheads can show better performance. ADMET analysis displays that our selected candidates appear to be safer inhibitors. Our combined studies suggest that the best cysteine focused ligands can help to design an effective lead drug for COVID-19 treatment. Communicated by Ramaswamy H. Sarma.


Assuntos
Proteases 3C de Coronavírus/antagonistas & inibidores , Inibidores de Proteases , SARS-CoV-2 , COVID-19 , Cisteína , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Relação Estrutura-Atividade , Tratamento Farmacológico da COVID-19
3.
Comput Biol Med ; 134: 104492, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34022487

RESUMO

Dengue, a mosquito-borne disease, has appeared as a major infectious disease globally. The virus requires its proteins to replicate and reproduce in the host cell. The NS3 protease converts the polyprotein to functional proteins with the help of the NS2B cofactor. Thus, NS3 protease is a promising target to develop antiviral inhibitors against the dengue virus. A systematic screening including ADMET properties, molecular docking, molecular dynamics (MD) simulation, binding free energy calculation, and QSAR studies is carried out to predict potent inhibitors against the NS3 protease. From the screening of 40 antiviral phytochemicals, ADMET properties analysis was used to screen out ligands that violate ADME rules and have probable toxicity. Cyanidin 3-Glucoside, Dithymoquinone, and Glabridin were predicted to be potent inhibitors against the NS3 protease according to their binding affinity. These ligands showed several noncovalent interactions, including hydrogen bond, hydrophobic interaction, electrostatic interaction, pi-sulfur interactions. The ligand-protein complexes were further scrutinized using 250 ns molecular dynamics simulation. The MM-PBSA binding free energy calculation was conducted to investigate their binding stability in dynamic conditions. The calculated pIC50(mM) value was predicted using the QSAR model with 89.91% goodness of fit. The predicted biologocal activity value for the ligands indicates they might have good potency.


Assuntos
Vírus da Dengue , Animais , Antivirais/farmacologia , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Compostos Fitoquímicos/farmacologia , Inibidores de Proteases/farmacologia
4.
J Biomol Struct Dyn ; 39(9): 3213-3224, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340562

RESUMO

The main protease of SARS-CoV-2 is one of the important targets to design and develop antiviral drugs. In this study, we have selected 40 antiviral phytochemicals to find out the best candidates which can act as potent inhibitors against the main protease. Molecular docking is performed using AutoDock Vina and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the main protease. The selected candidates strongly interact with the key Cys145 and His41 residues. To validate the docking interactions, 100 ns molecular dynamics (MD) simulations on the five top-ranked inhibitors including hypericin, cyanidin 3-glucoside, baicalin, glabridin, and α-ketoamide-11r are performed. Principal component analysis (PCA) on the MD simulation discloses that baicalin, cyanidin 3-glucoside, and α-ketoamide-11r have structural similarity with the apo-form of the main protease. These findings are also strongly supported by root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA) investigations. PCA is also used to find out the quantitative structure-activity relationship (QSAR) for pattern recognition of the best ligands. Multiple linear regression (MLR) of QSAR reveals the R2 value of 0.842 for the training set and 0.753 for the test set. Our proposed MLR model can predict the favorable binding energy compared with the binding energy detected from molecular docking. ADMET analysis demonstrates that these candidates appear to be safer inhibitors. Our comprehensive computational and statistical analysis show that these selected phytochemicals can be used as potential inhibitors against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , SARS-CoV-2 , Antivirais/farmacologia , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Compostos Fitoquímicos/farmacologia
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