In the context of recently emerged pandemic of COVID-19, we have performed two-dimensional quantitative structure-activity relationship (2D-QSAR) modelling using SARS-CoV-3CLpro enzyme inhibitors for the development of a multiple linear regression (MLR) based model. We have used 2D descriptors with an aim to develop an easily interpretable, transferable and reproducible model which may be used for quick prediction of SAR-CoV-3CLpro inhibitory activity for query compounds in the screening process. Based on the insights obtained from the developed 2D-QSAR model, we have identified the structural features responsible for the enhancement of the inhibitory activity against 3CLpro enzyme. Moreover, we have performed the molecular docking analysis using the most and least active molecules from the dataset to understand the molecular interactions involved in binding, and the results were then correlated with the essential structural features obtained from the 2D-QSAR model. Additionally, we have performed in silico predictions of SARS-CoV 3CLpro enzyme inhibitory activity of a total of 50,437 compounds obtained from two anti-viral drug databases (CAS COVID-19 antiviral candidate compound database and another recently reported list of prioritized compounds from the ZINC15 database) using the developed model and provided prioritized compounds for experimental detection of their performance for SARS-CoV 3CLpro enzyme inhibition.

In the context of recently emerged pandemic of COVID-19, we have performed two-dimensional quantitative structure-activity relationship (2D-QSAR) modelling using SARS-CoV-3CLpro enzyme inhibitors for the development of a multiple linear regression (MLR) based model. We have used 2D descriptors with an aim to develop an easily interpretable, transferable and reproducible model which may be used for quick prediction of SAR-CoV-3CLpro inhibitory activity for query compounds in the screening process. Based on the insights obtained from the developed 2D-QSAR model, we have identified the structural features responsible for the enhancement of the inhibitory activity against 3CLpro enzyme. Moreover, we have performed the molecular docking analysis using the most and least active molecules from the dataset to understand the molecular interactions involved in binding, and the results were then correlated with the essential structural features obtained from the 2D-QSAR model. Additionally, we have performed in silico predictions of SARS-CoV 3CLpro enzyme inhibitory activity of a total of 50,437 compounds obtained from two anti-viral drug databases (CAS COVID-19 antiviral candidate compound database and another recently reported list of prioritized compounds from the ZINC15 database) using the developed model and provided prioritized compounds for experimental detection of their performance for SARS-CoV 3CLpro enzyme inhibition.

ABSTRACT: Pesticides are applied all over the world to protect plants from pests. However, their application also causes toxicity to plants, which negatively affects the growth and development of plants. Pesticide toxicity results in reduction of chlorophyll and protein contents, accompanied by decreased photosynthetic efficiency of plants. Pesticide stress also generates reactive oxygen species which causes oxidative stress to plants. To attenuate the negative effects of oxidative stress, the antioxidative defense system of plants gets activated, and it includes enzymatic antioxidants as well as non-enzymatic antioxidants. The present review gives an overview of various physiological responses of plants under pesticide toxicity in tabulated form.

ABSTRACT: Pesticides are applied all over the world to protect plants from pests. However, their application also causes toxicity to plants, which negatively affects the growth and development of plants. Pesticide toxicity results in reduction of chlorophyll and protein contents, accompanied by decreased photosynthetic efficiency of plants. Pesticide stress also generates reactive oxygen species which causes oxidative stress to plants. To attenuate the negative effects of oxidative stress, the antioxidative defense system of plants gets activated, and it includes enzymatic antioxidants as well as non-enzymatic antioxidants. The present review gives an overview of various physiological responses of plants under pesticide toxicity in tabulated form.

We have developed a robust quantitative structure–activity relationship (QSAR) model employing a dataset of 98 heterocycle compounds to identify structural features responsible for BACE1 (beta-secretase 1) enzyme inhibition. We have used only 2D descriptors for model development purpose thus avoiding the conformational complications arising due to 3D geometry considerations. Following the strict Organization for Economic Co-operation and Development (OECD) guidelines, we have developed models using stepwise regression analysis followed by the best subset selection, while the final model was developed by partial least squares regression technique. The model was validated using various internationally accepted stringent validation parameters. From the insights obtained from the developed model, we have concluded that heteroatoms (nitrogen, oxygen, etc.) present within to an aromatic nucleus and the structural features such as hydrophobic, ring aromatic and hydrogen bond acceptor/donor are responsible for the enhancement of the BACE1 enzyme inhibitory activity. Moreover, we have performed the pharmacophore modelling to unveil the structural requirements for the inhibitory activity against the BACE1 enzyme. Furthermore, molecular docking studies were carried out to understand the molecular interactions involved in binding, and the results are then correlated with the requisite structural features obtained from the QSAR and pharmacophore models.

We have developed a robust quantitative structure–activity relationship (QSAR) model employing a dataset of 98 heterocycle compounds to identify structural features responsible for BACE1 (beta-secretase 1) enzyme inhibition. We have used only 2D descriptors for model development purpose thus avoiding the conformational complications arising due to 3D geometry considerations. Following the strict Organization for Economic Co-operation and Development (OECD) guidelines, we have developed models using stepwise regression analysis followed by the best subset selection, while the final model was developed by partial least squares regression technique. The model was validated using various internationally accepted stringent validation parameters. From the insights obtained from the developed model, we have concluded that heteroatoms (nitrogen, oxygen, etc.) present within to an aromatic nucleus and the structural features such as hydrophobic, ring aromatic and hydrogen bond acceptor/donor are responsible for the enhancement of the BACE1 enzyme inhibitory activity. Moreover, we have performed the pharmacophore modelling to unveil the structural requirements for the inhibitory activity against the BACE1 enzyme. Furthermore, molecular docking studies were carried out to understand the molecular interactions involved in binding, and the results are then correlated with the requisite structural features obtained from the QSAR and pharmacophore models.

Additional file 2. Additional data.

Additional file 2. Additional data.

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