Discovery of Bifunctional Anti-DPP-IV and Anti-ACE Peptides from Housefly Larval Proteins After In silico Gastrointestinal Digestion

Proteins and peptides of housefly larvae (HFL) have potential applications in food and therapy. The fate of HFL proteins following human gastrointestinal (GI) digestion is unknown. This study adopted a computational approach to discover peptides released from HFL proteins upon GI digestion. In silico digestion of eight major HFL proteins released 783 peptides. This comprised 243 peptides exhibiting 13 types of bioactivities. Ninety-two single-function peptides exhibiting anti-dipeptidyl peptidase IV (anti-DPP-IV), anti-dipeptidyl peptidase III, anti-angiotensin converting enzyme (anti-ACE), or antioxidant activity were found. Sixty-three multi-function peptides, encompassing 32 bifunctional anti-DPP-IV and anti-ACE peptides, were found. Further screening led to five non-toxic, non-allergenic, high-GI-absorption bifunctional dipeptides: AF, GW, GY, PH, and VF. Molecular docking found the dipeptides to interact with the active site of DPP-IV through hydrophobic interactions. Only GW and VF could bind to the active site of ACE. Thus, the five dipeptides are competitive inhibitors of DPP-IV. GW and VF are potential competitive inhibitors of ACE, whereas AF, GY, and PH are non-competitive inhibitors. Overall, GI digestion could liberate numerous single- and multi-function peptides from HFL proteins. Hence, HFL proteins can be tapped for potential applications in antidiabetic and antihypertension functional food and therapy.

Antiviral Activity of Two Marine Carotenoids against SARS-CoV-2 Virus Entry In Silico and In Vitro

The marine carotenoids fucoxanthin and siphonaxanthin are powerful antioxidants that are attracting focused attention to identify a variety of health benefits and industry applications. In this study, the binding energy of these carotenoids with the SARS-CoV-2 Spike-glycoprotein was predicted by molecular docking simulation, and their inhibitory activity was confirmed with SARS-CoV-2 pseudovirus on HEK293 cells overexpressing angiotensin-converting enzyme 2 (ACE2). Siphonaxanthin from Codium fragile showed significant antiviral activity with an IC50 of 87.4 μM against SARS-CoV-2 pseudovirus entry, while fucoxanthin from Undaria pinnatifida sporophyll did not. The acute toxicities were predicted to be relatively low, and pharmacokinetic predictions indicate GI absorption. Although further studies are needed to elucidate the inhibition of viral infection by siphonaxanthin, these results provide useful information in the application of these marine carotenoids for the treatment and prevention of COVID-19.

Canthin-6-One 9-O-Beta-Glucopyranoside: an inhibitor of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/ 3CLpro

The rapid spread of SARS-CoV-2 has raised a severe global public health issue, where therapy is not identified with specific drugs or vaccines. The present investigation dealt with the inhibition of various proteins and receptors of virus using phytocompounds of three pertinent medicinal plants i.e. Eurycoma harmandiana, Sophora flavescens and Andrographis paniculata. Phytocompounds known to have antiviral properties were screened against the papain-like protease (PLpro) and main protease (Mpro) / 3-chymotrypsin-like Protease (3CLpro). Molecular docking with Canthin-6-One 9-O-Beta-Glucopyranoside showed the highest binding affinity and least binding energy with both the proteases viz. PLpro and Mpro/ 3CLpro. ADMET analysis of the compound suggested that it is having drug-like properties like high gastrointestinal (gi-) absorption, no blood-brain barrier permeability, and high lipophilicity.

Prediction of No Tropic Properties of Novel Drug Modafiendz using in-Silico Method

The development and approval of new drug is a tedious, expensive and highly time-consuming task. The demand of new drugs is increasing, and the development of natural drugs and traditional drugs are re-emerging as a new strategic task. The in-silico techniques have boosted the development of potential drug candidates. One important category of drugs is nootropes. It improves the cognitive function, memory, motivation and creativity in healthy individuals. The demand of the nootropic drugs has skyrocketed in past few decades. Modafiendz is a novel drug that is often used by the consumers as it is having similarity in structure and property with modafinil (Nootropic drug). But no major studies have been carried out on this molecule, so remains an investigatory molecule. There are several in-silico techniques that can be used to predict the likeness, metabolic activity and pharmacological property of a molecule. In the current study, realizing the importance of modafiendz, various properties of modafiendz have been predicted like metabolism site, ADME properties, metabolite prediction and DNA adduct formation tendencies.The properties of modafiendz were found to be similar to modafinil in various regards of drug likeability, bioavailability, blood brain permeability (BBB), GI absorption and site of metabolism (SOM). The study suggests modafiendz as a better nootropic drug candidate, when compared to modafinil.

New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties

The purpose of this work was to prepare Schiff base ligands containing quinoline moiety and using them for preparing Cu(ii) and Zn(ii) complexes. Four bidentate Schiff base ligands (SL1–SL4) with quinoline hydrazine scaffold and a series of mononuclear Cu(ii) and Zn(ii) complexes were successfully prepared and characterized. The in vitro antibacterial and antifungal potential experimentation revealed that the ligands exhibited moderate antibacterial activity against the Gram-positive bacterial types and were inactive against the Gram-negative bacteria and the fungus strains. The metal complexes showed some enhancement in the activity against the Gram-positive bacterial strains and were inactive against the Gram-negative bacteria and the fungus strains similar to the parent ligands. The complex [Cu(SL1)2] was the most toxic compound against both Gram-positive S. aureus and E. faecalis bacteria. The in silico physicochemical investigation revealed that the ligand SL4 showed highest in silico absorption (82.61%) and the two complexes [Cu(SL4)2] and [Zn(SL4)2] showed highest in silico absorption with 56.23% for both compounds. The in silico pharmacokinetics predictions showed that the ligands have high gastrointestinal (GI) absorption and the complexes showed low GI absorption. The ligands showed a good bioavailability score of 0.55 where the complexes showed moderate to poor bioavailability.

Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches

The main objective of this review is to discuss recent advancements in the overall investigation and in vivo prediction of drug absorption. The intestinal permeability of an orally administered drug (given the value Peff) has been widely used to determine the rate and extent of the drug’s intestinal absorption (Fabs) in humans. Preclinical gastrointestinal (GI) absorption models are currently in demand for the pharmaceutical development of novel dosage forms and new drug products. However, there is a strong need to improve our understanding of the interplay between pharmaceutical, biopharmaceutical, biochemical, and physiological factors when predicting Fabs and bioavailability. Currently, our knowledge of GI secretion, GI motility, and regional intestinal permeability, in both healthy subjects and patients with GI diseases, is limited by the relative inaccessibility of some intestinal segments of the human GI tract. In particular, our understanding of the complex and highly dynamic physiology of the region from the mid-jejunum to the sigmoid colon could be significantly improved. One approach to the assessment of intestinal permeability is to use animal models that allow these intestinal regions to be investigated in detail and then to compare the results with those from simple human permeability models such as cell cultures. Investigation of intestinal drug permeation processes is a crucial biopharmaceutical step in the development of oral pharmaceutical products. The determination of the intestinal Peff for a specific drug is dependent on the technique, model, and conditions applied, and is influenced by multiple interactions between the drug molecule and the biological membranes.

DESIGN AND CHARACTERIZATION OF NOVEL EMULGEL FOR PAIN MANAGEMENT

Topical DDS is a localized system preferred for drugs having hurdles like first pass metabolism through gastro intestinal absorption, reduced bioavailability, relatively short residence time and dose dumping. To provide continuous percutaneous absorption of drug at controlled rate which overcomes problems associated with GI absorption for oral DDS, semisolid formulations like cream, ointment and gel were preferred in topical DDS applied on skin. Amongst them gels having more aqueous portion have greater dissolution of drug. But these properties are suitable for hydrophilic drugs and not for hydrophobic drugs. This problem was solved by formulating an emulgel in which hydrophobic drugs can be incorporated in gel and used for topical application. The aim of this work was to develop emulgel of acelofenac a hydrophobic drug using Carbapol 940 as gelling agent and clove oil and mentha oil as penetration enhancers. Another aim was to investigate effect of concentration and formulation parameters on spreading coefficient drug release and viscosity of prepared emulgel.