Insight into the Hantaan virus RNA-dependent RNA polymerase inhibition using in-silico approaches.

The Hantaan virus (HTN) is a member of the hantaviridae family. It is a segmented type, negative-strand virus (sNSVs). It causes hemorrhagic fever with renal syndrome, which includes fever, vascular hemorrhage, and renal failure. This illness is one of the most serious hemorrhagic diseases in the world, and it is a major public health concern due to its high mortality rate. The Hantaan virus RNA-dependent RNA polymerase complex (RdRp) is involved in viral RNA transcription and replication for the survival and transmission of this virus. Therefore, it is a primary target for antiviral drug development. Interference with the endonucleolytic "cap-snatching" reaction by the HTN virus RdRp endonuclease domain is a particularly appealing approach for drug discovery against this virus. This RdRp endonuclease domain of the HTN virus has a metal-dependent catalytic activity. We targeted this metal-dependent enzymatic activity to identify inhibitors that can bind and disrupt this endonuclease enzyme activity using in-silico approaches i.e., molecular docking, molecular dynamics simulation, predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) and drug-likeness studies. The docking studies showed that peramivir, and ingavirin compounds can effectively bind with the manganese ions and engage with other active site residues of this protein. Molecular simulations also showed stable binding of these ligands with the active site of HTN RdRp. Simulation analysis showed that they were in constant contact with the active site manganese ions and amino acid residues of the HTN virus endonuclease domain. This study will help in better understanding the HTN and related viruses.

Chemical and Nutritional Profiling of the Seaweed Dictyota dichotoma and Evaluation of Its Antioxidant, Antimicrobial and Hypoglycemic Potentials.

Seaweed has been known to possess beneficial effects forhuman health due to the presence of functional bioactive components. The n-butanol and ethyl acetate extracts of Dictyota dichotoma showed ash (31.78%), crude fat (18.93%), crude protein (14.5%), and carbohydrate (12.35%) contents. About 19 compounds were identified in the n-butanol extract, primarily undecane, cetylic acid, hexadecenoic acid, Z-11-, lageracetal, dodecane, and tridecane, whereas 25 compounds were identified in the ethyl acetate extract, mainly tetradecanoic, hexadecenoic acid, Z-11-, undecane, and myristic acid. FT-IR spectroscopy confirmed the presence of carboxylic acid, phenols, aromatics, ethers, amides, sulfonates, and ketones. Moreover, total phenolic contents (TPC) and total flavonoid contents (TFC) in ethyl acetate extract were 2.56 and 2.51 mg GAE/g and in n-butanol extract were 2.11 and 2.25 mg QE/g, respectively. Ethyl acetate and n-butanol extracts at a high concentration of 100 mg mL-1 showed 66.64 and 56.56 % inhibition of DPPH, respectively. Antimicrobial activity revealed that Candida albicans was the most susceptible microorganism, followed by Bacillus subtilis, Staphylococcus aureus, and Escherichia coli, whereas Pseudomonas aeruginosa showed the least inhibition at all concentrations. The in vivo hypoglycemic study revealed that both extracts exhibited concentration-dependent hypoglycemic activities. In conclusion, this macroalgae exhibited antioxidant, antimicrobial, and hypoglycemic potentials.

Exploring the hidden treasures of Nitella hyalina: a comprehensive study on its biological compounds, nutritional profile, and unveiling its antimicrobial, antioxidative, and hypoglycemic properties.

Macroalgae has the potential to be a precious resource in food, pharmaceutical, and nutraceutical industries. Therefore, the present study was carried out to identify and quantify the phyco-chemicals and to assess the nutritional profile, antimicrobial, antioxidant, and anti-diabetic properties of Nitella hyalina extracts. Nutritional composition revealed0.05 ± 2.40% ash content, followed by crude protein (24.66 ± 0.95%), crude fat (17.66 ± 1.42%), crude fiber (2.17 ± 0.91%), moisture content (15.46 ± 0.48%) and calculated energy value (173.50 ± 2.90 Kcal/100 g). 23 compounds were identified through GC-MS analysis in ethyl acetate extract, with primary compounds being Palmitic acid, methyl ester, (Z)-9-Hexadecenoic acid, methyl ester, and Methyl tetra decanoate. Whereas 15 compounds were identified in n-butanol extract, with the major compounds being Tetra decanoic acid, 9-hexadecanoic acid, Methyl pentopyranoside, and undecane. FT-IR spectroscopy confirmed the presence of alcoholic phenol, saturated aliphatic compounds, lipids, carboxylic acid, carbonyl, aromatic components, amine, alkyl halides, alkene, and halogen compounds. Moreover, n-butanol contains 1.663 ± 0.768 mg GAE/g, of total phenolic contents (TPC,) and 2.050 ± 0.143 QE/g of total flavonoid contents (TFC), followed by ethyl acetate extract, i.e. 1.043 ± 0.961 mg GAE/g and 1.730 ± 0.311 mg QE/g respectively. Anti-radical scavenging effect in a range of 34.55-46.35% and 35.39-41.79% was measured for n-butanol and ethyl acetate extracts, respectively. Antimicrobial results declared that n-butanol extract had the highest growth inhibitory effect, followed by ethyl acetate extract. Pseudomonas aeruginosa was reported to be the most susceptible strain, followed by Staphylococcus aureus and Escherichia coli, while Candida albicans showed the least inhibition at all concentrations. In-vivo hypoglycemic study revealed that both extracts exhibited dose-dependent activity. Significant hypoglycemic activity was observed at a dose of 300 mg/kg- 1 after 6 h i.e. 241.50 ± 2.88, followed by doses of 200 and 100 mg/kg- 1 (245.17 ± 3.43 and 250.67 ± 7.45, respectively) for n-butanol extract. In conclusion, the macroalgae demonstrated potency concerning antioxidant, antimicrobial, and hypoglycemic properties.

Density-functional theory of the catnip molecule, nepetalactone.

Nepetalactones belongs to the group of iridoid monoterpenoids, which are present in the aerial parts of nepeta plants. Nepetalactone is an attractant to feline animals causing euphoric effects, while it is a repellent to mosquitoes and cockroaches. It is also a pheromone for several insect aphid species. The main objective of this research was to study the electronic and spectral properties of nepetalactones. We investigated its structural properties using hybrid density-functional theory of B3LYP and WB97XD functional with the 6-311++G(d,p) basis set to optimize the geometry, and then computed the electronic structure, HOMO-LUMO, natural bond orbitals, molecular electronic potential and its contour map. We also obtained spectral signatures of NMR, IR and UV-Vis, and compared them with experimental data from the literature. The DFT study provided different electronic and spectral information that will be of value for further research on making new derivatives of nepetalactones for commercial purposes. Nepetalactones have a promising future in the development of novel mosquito repellents for the control of malaria and arboviral diseases.

Photosystem II oxygen-evolving complex photoassembly displays an inverse H/D solvent isotope effect under chloride-limiting conditions.

Photosystem II (PSII) performs the solar-driven oxidation of water used to fuel oxygenic photosynthesis. The active site of water oxidation is the oxygen-evolving complex (OEC), a Mn4CaO5 cluster. PSII requires degradation of key subunits and reassembly of the OEC as frequently as every 20 to 40 min. The metals for the OEC are assembled within the PSII protein environment via a series of binding events and photochemically induced oxidation events, but the full mechanism is unknown. A role of proton release in this mechanism is suggested here by the observation that the yield of in vitro OEC photoassembly is higher in deuterated water, D2O, compared with H2O when chloride is limiting. In kinetic studies, OEC photoassembly shows a significant lag phase in H2O at limiting chloride concentrations with an apparent H/D solvent isotope effect of 0.14 ± 0.05. The growth phase of OEC photoassembly shows an H/D solvent isotope effect of 1.5 ± 0.2. We analyzed the protonation states of the OEC protein environment using classical Multiconformer Continuum Electrostatics. Combining experiments and simulations leads to a model in which protons are lost from amino acid that will serve as OEC ligands as metals are bound. Chloride and D2O increase the proton affinities of key amino acid residues. These residues tune the binding affinity of Mn2+/3+ and facilitate the deprotonation of water to form a proposed µ-hydroxo bridged Mn2+Mn3+ intermediate.

Prokinetic and Laxative Effects of Chrozophora tinctoria Whole Plant Extract.

Chrozophora tinctoria (Euphorbiaceae) has been used as an emetic, anthelminthic, and cathartic agent in traditional medicine. We used gas chromatography-mass spectrometry (GC-MS) to characterize the composition of ethyl acetate (EAC) and dichloromethane (DCMC) fractions from the whole Chrozophora tinctoria plant. EAC and DCMC fractions were evaluated for acetylcholinesterase (AChE) inhibitory activity and acute toxicity. Their effects on intestinal propulsive movement and spasmogenic activity of the gastrointestinal tract (GIT) muscle were also assessed. The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAC and 10 in DCMC. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant. Both EAC and DCMC fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5 g or higher and lethargy and mortality from 3-5 g upwards. Similarly, both of the fractions showed laxative activity in metronidazole- and loperamide-induced constipation models. EAC relaxed the intestinal muscle at a lower dose (1 mg/mL) than DCMC. Similarly, the EAC extract showed a significant relaxation effect (EC50 = 0.67 ± 0.15 mg/mL) on KCL-induced contraction in rabbit jejunum as compared to DCMC (EC50 = 5.04 ± 0.05 mg/kg). The present study strongly supports the folklore that this valuable plant is a cathartic agent. Further work is required to isolate and validate the bioactive compounds that act as diarrheal agents in Chrozophora tinctoria.

Extraction and Fractionation of Prokinetic Phytochemicals from Chrozophora tinctoria and Their Bioactivities.

Chrozophora tinctoria is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of Chrozophora tinctoria (MEC) whole plant and an n-butanol fraction of Chrozophora tinctoria (NBFC) were analyzed by gas chromatography-mass spectrometry (GC-MS) to detect the phytochemicals. MEC and NBFC were tested for in vitro anti acetylcholinesterase (AChE) potential. The effect of both samples on intestinal propulsive movement and spasmolytic activity in the gastrointestinal tract (GIT) was also studied. About twelve compounds in MEC and three compounds in NBFC were tentatively identified through GC-MS. Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid. Both NBFC and MEC samples were checked for acute toxicity and were found to be highly toxic in a dose-dependent manner, causing diarrhea and emesis at 1 g/kg concentration in pigeons, with the highest lethargy and mortality above 3 g/kg. Both the samples of Chrozophora tinctoria revealed significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation. NBFC (81.18 ± 2.5%) and MEC (68.28 ± 2.4%) significantly increased charcoal meal intestinal transit compared to distal water (41.15 ± 4.3%). NBFC exhibited a significant relaxant effect (EC50 = 3.40 ± 0.20 mg/mL) in spontaneous rabbit jejunum as compared to MEC (EC50 = 4.34 ± 0.68 mg/kg). Similarly, the impact of NBFC on KCl-induced contraction was more significant than that of MEC (EC50 values of 7.22 ± 0.06 mg/mL and 7.47 ± 0.57 mg/mL, respectively). The present study scientifically validates the folk use of Chrozophora tinctoria in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in Chrozophora tinctoria.

Identification and Inhibition of the Druggable Allosteric Site of SARS-CoV-2 NSP10/NSP16 Methyltransferase through Computational Approaches.

Since its emergence in early 2019, the respiratory infectious virus, SARS-CoV-2, has ravaged the health of millions of people globally and has affected almost every sphere of life. Many efforts are being made to combat the COVID-19 pandemic's emerging and recurrent waves caused by its evolving and more infectious variants. As a result, novel and unexpected targets for SARS-CoV-2 have been considered for drug discovery. 2'-O-Methyltransferase (nsp10/nsp16) is a significant and appealing target in the SARS-CoV-2 life cycle because it protects viral RNA from the host degradative enzymes via a cap formation process. In this work, we propose prospective allosteric inhibitors that target the allosteric site, SARS-CoV-2 MTase. Four drug libraries containing ~119,483 compounds were screened against the allosteric site of SARS-CoV-2 MTase identified in our research. The identified best compounds exhibited robust molecular interactions and alloscore-score rankings with the allosteric site of SARS-CoV-2 MTase. Moreover, to further assess the dynamic stability of these compounds (CHEMBL2229121, ZINC000009464451, SPECS AK-91811684151, NCI-ID = 715319), a 100 ns molecular dynamics simulation, along with its holo-form, was performed to provide insights on the dynamic nature of these allosteric inhibitors at the allosteric site of the SARS-CoV-2 MTase. Additionally, investigations of MM-GBSA binding free energies revealed a good perspective for these allosteric inhibitor-enzyme complexes, indicating their robust antagonistic action on SARS-CoV-2 (nsp10/nsp16) methyltransferase. We conclude that these allosteric repressive agents should be further evaluated through investigational assessments in order to combat the proliferation of SARS-CoV-2.

Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition.

The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. Simulation analyses confirmed that they are in constant contact during the simulation time course and have strong association with the enzyme's allosteric site. Absorption, distribution, metabolism, excretion and toxicity (ADMET) data provided medicinal information of these top three hits. They had good human intestinal absorption (HIA) concentrations and were non-toxic. Due to high mutation rates in the active sites of the viral enzyme, these new allosteric site inhibitors offer opportunities to drug SARS-CoV-2 RdRp. These results provide new information for the design of novel allosteric inhibitors against SARS-CoV-2 RdRp.

Isolation, Characterization, and Medicinal Potential of Polysaccharides of Morchella esculenta.

Mushroom polysaccharides are active medicinal compounds that possess immune-modulatory and anticancer properties. Currently, the mushroom polysaccharides krestin, lentinan, and polysaccharopeptides are used as anticancer drugs. They are an unexplored source of natural products with huge potential in both the medicinal and nutraceutical industries. The northern parts of Pakistan have a rich biodiversity of mushrooms that grow during different seasons of the year. Here we selected an edible Morchella esculenta (true morels) of the Ascomycota group for polysaccharide isolation and characterization. Polysaccharopeptides and polysaccharides from this mushroom were isolated using the green chemistry, hot water treatment method. Fourier transform infrared spectroscopy revealed the sugar nature and possible beta-glucan type structure of these polysaccharides. Antioxidant assays showed that the deproteinized polysaccharides have moderate free radical scavenging activity. These isolated polysaccharides exhibited good acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) inhibition activities. Therefore, these polysaccharides may be valuable for the treatment of Alzheimer's and Parkinson's diseases. Further bioassays are needed to discover the true potential of M. esculenta polysaccharides for medicinal purposes.

Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins.

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.

Important Flavonoids and Their Role as a Therapeutic Agent.

Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations.

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of flaviviruses are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through in-vitro and in-vivo studies.

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives.

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.

Mutations in algal and cyanobacterial Photosystem I that independently affect the yield of initial charge separation in the two electron transfer cofactor branches.

In Photosystem I, light-induced electron transfer can occur in either of two symmetry-related branches of cofactors, each of which is composed of a pair of chlorophylls (ec2A/ec3A or ec2B/ec3B) and a phylloquinone (PhQA or PhQB). The axial ligand to the central Mg2+ of the ec2A and ec2B chlorophylls is a water molecule that is also H-bonded to a nearby Asn residue. Here, we investigate the importance of this interaction for charge separation by converting each of the Asn residues to a Leu in the green alga, Chlamydomonas reinhardtii, and the cyanobacterium, Synechocystis sp. PCC6803, and studying the energy and electron transfer using time-resolved optical and EPR spectroscopy. Nanosecond transient absorbance measurements of the PhQ to FX electron transfer show that in both species, the PsaA-N604L mutation (near ec2B) results in a ~50% reduction in the amount of electron transfer in the B-branch, while the PsaB-N591L mutation (near ec2A) results in a ~70% reduction in the amount of electron transfer in the A-branch. A diminished quantum yield of P700+PhQ- is also observed in ultrafast optical experiments, but the lower yield does not appear to be a consequence of charge recombination in the nanosecond or microsecond timescales. The most significant finding is that the yield of electron transfer in the unaffected branch did not increase to compensate for the lower yield in the affected branch. Hence, each branch of the reaction center appears to operate independently of the other in carrying out light-induced charge separation.

Increasing the Strength and Production of Artemisinin and Its Derivatives.

Artemisinin is a natural sesquiterpene lactone obtained from the Artemisia annua herb. It is widely used for the treatment of malaria. In this article, we have reviewed the role of artemisinin in controlling malaria, spread of resistance to artemisinin and the different methods used for its large scale production. The highest amount of artemisinin gene expression in tobacco leaf chloroplast leads to the production of 0.8 mg/g of the dry weight of the plant. This will revolutionize the treatment and control of malaria in third world countries. Furthermore, the generations of novel derivatives of artemisinin- and trioxane ring structure-inspired compounds are important for the treatment of malaria caused by resistant plasmodial species. Synthetic endoperoxide-like artefenomel and its derivatives are crucial for the control of malaria and such synthetic compounds should be further explored.

Photosynthesis at the far-red region of the spectrum in Acaryochloris marina.

Acaryochloris marina is an oxygenic cyanobacterium that utilizes far-red light for photosynthesis. It has an expanded genome, which helps in its adaptability to the environment, where it can survive on low energy photons. Its major light absorbing pigment is chlorophyll d and it has α-carotene as a major carotenoid. Light harvesting antenna includes the external phycobilin binding proteins, which are hexameric rods made of phycocyanin and allophycocyanins, while the small integral membrane bound chlorophyll binding proteins are also present. There is specific chlorophyll a molecule in both the reaction center of Photosystem I (PSI) and PSII, but majority of the reaction center consists of chlorophyll d. The composition of the PSII reaction center is debatable especially the role and position of chlorophyll a in it. Here we discuss the photosystems of this bacterium and its related biology.

Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen.

The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain's length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles 1a-c with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of 1a-c with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and ¹H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives 1a-c were found to have a significant impact on the solubility of NAP and IBP in pure water.

Bioactive Thiazine and Benzothiazine Derivatives: Green Synthesis Methods and Their Medicinal Importance.

Thiazines are a group of heterocyclic organic compounds that are still largely unexplored for their pharmacological activities. There are different available methods for the synthesis of thiazine derivatives in the literature. In this review, we discuss available methods of thiazine preparation through green synthesis methods. Beside their synthesis, many thiazine derivatives are biologically active and play an important role in the treatment of various diseases and show promising results of varying degrees, where they act as antibacterial, antifungal, antitumor, antimalarial, antineoplastic, antiviral, anti-inflammatory, analgesic and anticancer agents and thus they represent an interesting class of heterocyclic medicinal compounds worthy of further exploration.

The Search for Covalently Ligandable Proteins in Biological Systems.

This commentary highlights the recent article published in Nature, June 2016, titled: "Proteome-wide covalent ligand discovery in native biological systems". They screened the whole proteome of different human cell lines and cell lysates. Around 700 druggable cysteines in the whole proteome were found to bind the electrophilic fragments in both active and inactive states of the proteins. Their experiment and computational docking results agreed with one another. The usefulness of this study in terms of bringing a change in medicinal chemistry is highlighted here.