A pandemic caused by the novel coronavirus (SARS-CoV-2 or COVID-19) began in December 2019 in Wuhan, China, and the number of newly reported cases continues to increase. More than 19.7 million cases have been reported globally and about 728,000 have died as of this writing (10 August 2020). Recently, it has been confirmed that the SARS-CoV-2 main protease (Mpro) enzyme is responsible not only for viral reproduction but also impedes host immune responses. The Mpro provides a highly favorable pharmacological target for the discovery and design of inhibitors. Currently, no specific therapies are available, and investigations into the treatment of COVID-19 are lacking. Therefore, herein, we analyzed the bioactive phytocompounds isolated by gas chromatography–mass spectroscopy (GC-MS) from Tinospora crispa as potential COVID-19 Mpro inhibitors, using molecular docking study. Our analyses unveiled that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules, with three of them exerting biological activity and warranting further optimization and drug development to combat COVID-19.

The existing therapeutic agents for the management of pain and pyrexia are not very efficient and accompanied by numerous side effects. Thus, new effective agents are the most needed. The present study investigates bioactivities and phytochemical screening of different parts of Cissus assamica (Vitaceae), a Bangladeshi tribal medicinal plant. Three plant parts stems, leaves and roots were collected, washed, dried, powdered and then prepared for cold extraction. The methanolic stems and leaves extracts were fractioned with four and two solvents respectively. Different plant extracts were then investigated for in vivo antinociceptive activity and only methanolic leaves extract was investigated for in vivo antipyretic activity. In Swiss-albino mice, 200 and 400 mg/kg body weight doses were used for all extracts. In the peripheral antinociceptive activity, the methanolic stem extract and its dichloromethane, chloroform, pet ether fractions and methanolic roots extract at their both doses showed significant antinociceptive responses when compared to standard diclofenac sodium (60.49% inhibition). In the central antinociceptive activity, the response was found significant for methanolic stem and methanolic roots extract in their both doses compared to standard morphine. In antipyretic activity, methanolic leaves extract significantly reduced pyrexia level at 400 and 200 mg/kg body weight doses after two, three and 4 h of administration when compared to standard. So our findings indicate that this plant possesses noteworthy pharmacological activities which may be a basis for further researches to establish a possible mode of action of its different parts.

Piper sylvaticum Roxb., (Family: Piperaceae), commonly known as pahaari peepal, is used in traditional medicine for the treatment of rheumatic pain, headache, asthma, chronic cough, diarrhea, and wounds. To provide scientiic proof for its traditional use, the present study was designed to investigate the antinociceptive and anti-inlammatory properties of methanol extract of P. sylvaticum stem (MEPSS) in pain models. Additionally, computational studies viz. molecular docking, ADME and toxicological property predictions were performed to identify the potent phytochemicals of this plant for antinociceptive and anti-inlammatory activities with good oral bioavailability and safety features. Quantitative phytochemical analysis of MEPSS was performed using established protocols. The antinociceptive activity was determined using acetic acid and formalin test in mice at the doses of 200 and 400 mg/kg while paw edema induced by carrageenan used for anti-inlammatory activity. Molecular docking study was performed by Schrödinger Maestro 10.1 whereas the SwissADME and admetSAR were used for ADME and toxicity prediction respectively. The total phenolic and lavonoid contents of MEPSS were 93.39 and 53.74 mg gallic acid and quercetin equivalent/g of extract respectively. The methanol extract exhibited signiicant and dosedependent antinociceptive and anti-inlammatory efects in experimental pain models. Also, our docking study showed that piperine, piperlonguminine, and sylvamide have the best binding ainities to cyclooxygenase enzymes with good ADME/T properties. This study conirmed that MEPSS possess signiicant antinociceptive and anti-inlammatory activities which could be due to the presence of phytochemicals and three bioactive compounds (piperine, piperlonguminine, and sylvamide) were found to be most efective in computational studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a contemporary coronavirus, has impacted global economic activity and has a high transmission rate. As a result of the virus’s severe medical effects, developing effective vaccinations is vital. Plant-derived metabolites have been discovered as potential SARS-CoV-2 inhibitors. The SARS-CoV-2 main protease (Mpro) is a target for therapeutic research because of its highly conserved protein sequence. Gas chromatography–mass spectrometry (GC-MS) and molecular docking were used to screen 34 compounds identified from Leucas zeylanica for potential inhibitory activity against the SARS-CoV-2 Mpro. In addition, prime molecular mechanics–generalized Born surface area (MM-GBSA) was used to screen the compound dataset using a molecular dynamics simulation. From molecular docking analysis, 26 compounds were capable of interaction with the SARS-CoV-2 Mpro, while three compounds, namely 11-oxa-dispiro[4.0.4.1]undecan-1-ol (−5.755 kcal/mol), azetidin-2-one 3,3-dimethyl-4-(1-aminoethyl) (−5.39 kcal/mol), and lorazepam, 2TMS derivative (−5.246 kcal/mol), exhibited the highest docking scores. These three ligands were assessed by MM-GBSA, which revealed that they bind with the necessary Mpro amino acids in the catalytic groove to cause protein inhibition, including Ser144, Cys145, and His41. The molecular dynamics simulation confirmed the complex rigidity and stability of the docked ligand–Mpro complexes based on the analysis of mean radical variations, root-mean-square fluctuations, solvent-accessible surface area, radius of gyration, and hydrogen bond formation. The study of the postmolecular dynamics confirmation also confirmed that lorazepam, 11-oxa-dispiro[4.0.4.1]undecan-1-ol, and azetidin-2-one-3, 3-dimethyl-4-(1-aminoethyl) interact with similar Mpro binding pockets. The results of our computerized drug design approach may assist in the fight against SARS-CoV-2.

Background: The present study was conducted to investigate the anthelmintic activity of methanol extract of Piper sylvaticum stem (MEPSS) in experimental model followed by in silico molecular docking study and ADME/T analysis. Methods: Anthelmintic activity was determined by an aquarium worm (Tubifex tubifex). Then, molecular docking study was performed to identify compounds having maximum activity against TUBULIN-COLCHICINE enzymes by using Schrödinger-Maestro v 10.1 docking fitness. Additionally, ADME/T profiles were checked by Swiss ADME Analysis and Molinspiration Cheminformatics software.

In many gram-negative bacteria, the type III secretion system (T3SS), as a virulence factor, is an attractive target for developing novel antibacterial. Regarding this, in our study, we aimed to identify the putative drug target for Pseudomonas aeruginosa, considering ATPase enzyme involved in the type III secretion system. Selective protein sequence of P. aeruginosa involved in the T3SS was retrieved from NCBI databases, and its homologues were subjected to phylogenetic analysis. Its association in T3SS was analyzed via STRING, and the 3D structure was determined by means of homology modeling followed by intensive optimization and validation. The binding site was predicted by 3DLigandSite and examined through molecular docking simulation by Autodock Vina with salicylidene acylhydrazide class of virulence-blocking compounds. PROCHECK analysis showed that 96.7 % of the residues were in the most favored regions, 1.9 % were in the additional allowed region, and 1.4 % were in the generously allowed region of the Ramachandran plot. The refined model yielded ERRAT scores of 88.124 and Verify3D value of 0.2, which indicates that the environmental profile of the model is good. The best binding affinity was observed by ME0055 compound, and ALA160, ALA161, GlY162, GLY163, GLY164, GLY165, SER166, THR167, TYR338, and PRO339 residues were found to be having complementary in the ligand-binding site. However, these findings should be further confirmed by wet lab studies for design a targeted therapeutic agent.

Background: Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values. The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro, in vivo and in silico models. Methods:The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark (MECVB) through in vitro, in vivo and in silico assays. Analgesic activity was tested using formalin-induced nociception and acetic acid-induced writhing assays while the antipyretic effect was tested using yeast-induced hyperthermia in mice model. The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay. In addition, in silico studies were conducted using computer aided methods. Results:In the acetic acid-induced writhing assay, the extract showed 28.36% and 56.16% inhibition of writhing for doses of 200 and 400 mg/kg, respectively. Moreover, a dose-dependent formalin-induced licking response was observed in both early and late phase. In yeast-induced pyrexia, the MECVB exhibited (p < 0.05) antipyretic effect. The extract demonstrated an IC 50 value of 78.86 μg/ml compared with ascorbic acid (IC 50 23.53 μg/ml) in the DPPH scavenging assay. The compounds sitosterol, 5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I (2OYE), COX-II (6COX) and human peroxiredoxin 5 (1HD2). In ADME/T analysis, 5,7-dimethoxycoumarin and scopoletin satisfied Lipinski's rule of five and thus are potential drug candidates. Conclusion:The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

Phoenix sylvestris (khejur palm) is a very graceful palm which is also known as Wild date palm, Silver date palm, date sugar palm and belongs to the family Arecaceae. The various parts of the plant reported possessing diuretic, analgesic effect, anti-inflammatory, antibacterial, thrombolytic and neuropharmacological activities. Phoenix sylvestris is traditionally claimed to have antidiabetic, antidiarrheal, anti-dysentery activity and used in the treatment of a toothache, menstrual complaint. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Phoenix sylvestris, namely 4-methylcatechol towards TISSUE PLASMINOGEN ACTI-VATOR for searching of the lead molecule against thrombus. A wide range of docking score found during molecular docking by Schrodinger. 4-methylcatechol and 2, 3-Dihydro-3,5dihydroxy-6-methyl-4H-pyran-4-one showed the docking score respectively -6.077kJ/mol and -5.378kJ/mol against TISSUE PLASMINOGEN ACTIVATOR. Between all the compounds 4-methylcatechol showed the best docking score towards TISSUE PLASMINOGEN ACTIVA-TOR. So, 4-methylcatechol is the best compound for TISSUE PLASMINOGEN ACTIVATOR enzyme inhibition, as it possessed the best value in Molecular Docking. Further, in vivo investigation needs to identify TISSUE PLASMINOGEN ACTIVATOR enzyme inhibitory activity of isolated compounds from Phoenix sylvestris.