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Background: Drug development strategies for treating COVID-19 focus on actives that either physically block angiotensin-converting enzyme-2 (ACE-2) receptors (viral entry point), or those, which inactivate viral proteases like 3CLpro or RdRp, inside the infected host cells. Objectives: The objective of the present study is to virtually screen phytochemicals for both these purposes. Methods: Molecular docking, molecular dynamic simulation (MDS) and multiple sequence alignment were employed. Results: All the screened phytochemical actives showed negative binding energies with their respective targets, attesting good complex stabilities. Among each set of ten actives, for blocking ACE-2 receptors and for inactivation of 3CLpro and RdRp, Dichamanetin-ACE-2, Glabrene-3CLpro and Naringenin-RdRp complexes were most stable, with binding energies of -9.8, -9.11 and -7.7 Kcal/mol respectively. MDS studies of these representative actives and their complexes, also attested to complex stabilities. Multiple sequence alignment analysis of nine significant amino acid residues of the Homo sapiens ACE-2 receptor, with nine different species, showed conservation of several residues. Conclusion: A set of phytochemicals actives can block ACE-2 receptors and prevent the entry of SARS-CoV-2 into host endothelial cells. Two other sets of actives can inactivate viral 3CLpro and RdRp enzymes and prevent replication of SARS-CoV-2 inside host cells. They all can hence be further explored for the control of COVID-19.

Favipiravir and remdesivir are investigational drugs for coronavirus disease 2019 that is caused by severe acute respiratory syndrome coronavirus 2. The active forms of these drugs are reported to target and inhibit viral RNA dependent RNA polymerase, which is derived from 3-chymotrypsin like protease, a viral replicase enzyme. The present in silico study explores the comparative efficacy of these drugs to inhibit 3-chymotrypsin like protease and RNA dependent RNA polymerase, to plan therapeutic options for patients based on their disease severity. Active favipiravir and remdesivir molecules bind to 3-chymotrypsin like protease with energies of 6.18 and -6.52 kcal/mol in contrast to -5.62 and -3.91 kcal/mol for RNA dependent RNA polymerase. Further, hydrophobic interactions and salt bridge formations cement drug bindings with 3-chymotrypsin like protease, but not with RNA dependent RNA polymerase. Molecular dynamic simulation experiments, performed under certain experimental constraints reveal that the root mean square flexibilities of active residues in drug complexes with 3-chymotrypsin like protease are lower than in free 3-chymotrypsin like protease making the former more stable than the latter because of their rigidity and stabilities. Both drugs may hence serve as good therapeutic options for early stages of coronavirus disease 2019. However, more severe symptoms may be treated better with favipiravir due to its better binding with RNA dependent RNA polymerase, as compared to remdesivir. The “one drug does not fit all” concept is true for coronavirus disease 2019 as it is being currently realized by clinicians all around the world. Hence precise knowledge about critical interactions of these drugs with the viral enzymes will help medicos make vital therapeutic decisions on interventional options for patients who report to hospitals without over symptoms or with varying degrees of disease severity.

Background Green formulations with herbal oils and natural nonionic emulsifiers project several advantages, like favorable viscosity profiles, for use as topical applicants. Their inherent constituents also protect the skin against free radical damage and lipid peroxidation. They may hence serve as alternatives for synthetic chemical-based formulations. Objective Formulation and characterization of Helianthus annuus-alkyl polyglucoside cream for topical application has been attempted. Its inherent sun protection factor has been measured and compared with a similar commercial formulation. It is well known that the internal network of liquid crystals of such emulsifiers can store depot water to maintain moisturization for long time, thus bestowing beneficial dermatological effects. Methods Physicochemical characterization of the oil was done. The formulation process for the cream was optimized for reduced particle size with respect to ultrasonication conditions. It was characterized extensively; its inherent sun protection factor was measured and compared with a similar commercial cream. Results The cream was smooth, creamy, and showed non-Newtonian thixotropic behavior and good shear-thinning features with an SPF of 6.3 that compared favorably with a similar commercial cream. Conclusions The cream may serve as a good topical applicant and also help in skin hydration due to the inherent nature of the emulsifier. It may protect against UV radiations due to the antioxidant and anti-inflammatory nature of the natural oil constituents. It may be used as a low-SPF formulation.

Acid red 2 is a mono azo dye that adversely affects the environment when discharged into industrial effluents. This study investigates remediation of acid red 2 using alumina nanoparticles and Klebsiella pneumoniae. Decolorization assays at 521 nm were carried out using pure 24 hour bacterial culture, with nanoparticles and bacteria-nanoparticle mixture for 4 hours. Results reveal that 20 mg of alumina nanoparticles decolorized only 23.95% of methyl red whereas 10 ml of bacterial culture combined with 20 mg of alumina nanoparticles decolorized 84.84% of acid red 2 (500 mg/L). The bacterial culture decolorized 79.98% of the dye. Immobilization of nanoparticles on bacteria and dye degradation were confirmed using SEM and FTIR analysis, respectively. Therefore, the synergistic action of alumina nanoparticles and Klebsiella pneumoniae can be exploited for nanoremediation of acid red 2.

Murraya koenigii Linn leaf (curry leaf) is a favored spice known for its medicinal, therapeutic, nutraceutical and cosmetic properties. Its oil formulations have emerged as a favorable base for controlled delivery of actives by topical route of administration. However, most of such formulations include several synthetic chemicals as emulsifiers and stabilizers that may be hazardous in the long run. In the present study, curry leaf oil formulation with an alkyl polyglucoside emulsifier has been formulated for potential dermatological applications. Ultrasonication was employed for reduced particle size and better efficiency. The formulation was characterized for mean particle size, polydispersity index zeta potential and electrophoretic mobility. FTIR analysis of the oil confirmed the presence of the functional groups of its constituents as identified by GC-MS and revealed the prevalence of extensive hydrogen bonding in the formulation. Its SEM image showed the structural topography. The viability of different concentrations of the oil, tested on dermal fibroblasts cells (3T3 cell lines), was found to be from 97% to 20%. The accelerated stability tests confirmed the formulation’s non-susceptibility to various destabilization mechanisms after a period of 180 days at 37 °C, or under low speed centrifugation. Furthermore, the formulation was stable when stored at 40 °C, 4 °C and −18 °C for 3 cycles. Thus, this bio based formulation can either be used as such or as a base matrix for loading active ingredients for topical delivery.

Constituents of Azadirachta indica A. Juss (neem), have antimicrobial, cell proliferative, anti-inflammatory and wound healing properties. In the present study, neem seed oil is emulsified with an alkyl polyglucoside, Montanov 202™, to produce a topical applicant with liquid crystals that ensconce depot as confirmed by polarised microscopic, thermal and WXRD studies. Anti-inflammatory investigations by paw edema model, with this topical applicant in female Wistar rats showed inhibition of paw swelling by 39–60% over 30–180 min when compared to untreated animals. Similarly, wounds induced by incision procedure also had a significantly higher breaking strength (353.46 ± 7.95 g) when treated with this applicant after induction. Further, upon similar application, contraction was significantly higher (95% by 16th day) in wounds induced by excision procedures, with a re-epithelization period of 10.21 ± 2.31 days. Histopathology of these skin sections showed accelerated healing with development of dermis/epidermis and collagen with results that were synchronous to neomycin treated positive control rats. This applicant was also able to inhibit the growth of methicillin resistant S. aureus strains as shown by in vitro studies. It is inferred that the depot water ensconced in its liquid crystals synergistically supports the bioactivity of neem oil constituents to aid the healing of topical wounds as effectually as synthetic antibiotics. Simultaneous protection against MRSA induced wound infections serves as an additional advantage of this neem oil topical applicant.

Emulsion formulations of essential oils are of major interest due to their relative biosafety, biocompatibility and good pharmacological potential. Their structural constituents (oil and water phase) facilitate ready solubilization of incorporated hydrophilic/lipophilic actives for their targeted delivery. In the present study, m5S cells were tested for their viability at various concentrations of clove oil and an alkyl polyglucoside emulsifier, viz., Montanov 202™. Thereafter, good cell viable concentrations of oil (10 %) and emulsifier (4%) were used at their optimised ratio (1:0.4) to formulate an oil in water emulsion using phase inversion technique followed by ultrasonication for particle size reduction. Gas chromatography-mass spectrometry (GC–MS) analysis of clove oil revealed eugenol (76.11 %) and eugenyl acetate (12.41 %) as major constituents. The formulated clove oil emulsion was then characterised with respect to its size, zeta potential, microscopic and thermal analysis and the presence of liquid crystals were observed in the same. It was further studied for its anti-inflammatory potential in female Wistar rats wherein topical treatment with the emulsion inhibited paw swelling induced by carrageenan model by 40−60% over 30−180 min compared to untreated animals. Similarly, the emulsion’s wound healing potential was also significant with respect to wounds induced by both incision (wound breaking strength of 338.91 ± 5.02 g) and excision (95 % wound contraction by 16th day) model in these animals, with a re-epithelization period of 10.67 ± 1.67 days and results being comparable with diclofenac gel and neomycin cream (positive controls). Histopathology of the skin sections showed accelerated healing with early granular tissue and collagen formation in emulsion treated animals. It is hence envisaged that this clove oil emulsion can substitute chemical based topical products for anti-inflammatory and wound healing applications due to its biological constituents as well as because of the presence of liquid crystals in its formulation.

Caries is a multifactorial infection that can be caused by Streptococcus mutans. This bacteria is responsible for the formation of oral biofilms and incorporates properties that is conducive for its survival in hostile oral environments. Long-term adverse effects like hypersensitivity reactions, supra-infections and teeth staining coupled with the risk of resistance-development limit use of chemical preparations and antibiotics for caries prevention. Hence plant-based formulations with substantial antimicrobial and anti-cariogenic properties, could serve as alternatives for caries prevention. In this study, a Cymbopogon citratus (lemongrass) oil-in-water emulsion with Tween80/Span80 was formulated and favorably characterized using particle size (252.3±1.15nm with polydispersity index of 0.111± 0.01), FTIR and AFM analyses and stability studies. Its MIC and the MIC of alumina nanoparticles against cultures and isolates of Streptococcus mutans was around 600ppm. However, with the alumina nanoparticle loaded emulsion, the MIC was observed at a much lower concentration of around 400ppm. This nanoparticle incorporated emulsion was also able to inhibit the biofilm formation, with the time kill assay showing a decrease in cell numbers within 60 to 120 minutes post incubation. Alumina incorporated lemon grass oil emulsion may thus to prevent dental caries induced by Streptococcus mutans.

Dimple R Bhatia,Padma Thiagarajan School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India Aim: This study reports the influence of hypoxia on response of colorectal cancer cells to anticancer effects of sorafenib in combination with PI3K inhibitors GDC-0941 and BEZ-235.Materials and methods: All hypoxic exposures were carried out at 1% O2/5% CO2. Antiproliferation activity was evaluated by 48hours propidium iodide and 14days clonogenic assay. Protein levels were evaluated by fluorescence ELISA. Metabolites lactate and glucose were evaluated biochemically.Results: In the 48-hour proliferation assay, sorafenib acted synergistically with GDC-0941 but not with BEZ-235. In long-term colony-forming assays, both GDC-0941 and BEZ-235 were shown to potentiate the antiproliferative activity of sorafenib. At the molecular level, the synergism is mediated through inhibition of pAKT, pS6, p4EBP1, pERK, cyclin D1, and Bcl-2. No change in hypoxia-inducible factor-1α (HIF-1α) levels was observed in cells treated with the combination of compounds under hypoxia. A significant reduction in glucose uptake and lactate release was observed in cells treated with the combination of compounds under normoxia and hypoxia.Conclusion: Combinations of sorafenib with PI3K inhibitors BEZ-235 and GDC-0941 are efficacious under hypoxia. Thus, these anticancer combinations have a potential to overcome the hypoxia-mediated resistance mechanisms to antiproliferative agents in cancer therapy. Keywords: GDC-0941, BEZ-235, anticancer, antiproliferation

Food items and plants are mostly affected by bacterial pathogens that results in spreading of infection among consumers of contaminated foods and also yield loss in agricultural crops respectively. An essential oil such as cedarwood oil extracted from Cedrus deodara has excellent insecticidal, pesticidal and antimicrobial activities. In the present study, surfactants Tween 20 and Span 80 were used for emulsifying cedarwood oil to produce an oil in water emulsion that was found to be stable for the observed period of 120 days. The emulsion was characterized extensively by zeta potential, electrophoretic mobility, conductivity, turbidity, microscopic and FTIR studies with favorable results. The activity of the oil and its emulsion was checked against the food and plant pathogens and good activity was observed against all organisms.

Azadirachta indica A. Juss (Neem) is attested to be an important medicinal tree whose parts and extracts are known to cure several ailments since the Vedic era. But knowledge regarding their concoctions and dosages has remained largely esoteric. Dilute neem oil emulsions are used to deliver active ingredients to body parts by the topical route of administration. This possibly attenuates its dose dumping and concentration related noxious effects to a large extent. However, almost all such products incorporate synthetic organic and bio hazardous chemicals for purposes of formulation and stability, posing ultimate risks to the user. Hence in the present study, an emollient cream using 10% neem oil and an arachidyl glucoside emulsifier of completely biological origin has been formulated. Octa and hexadecanoic acid derivatives were the major fatty acid components identified in the oil. The creamy white product showed a mean particle size of 137 nm and a Z average of 19 nm, with a polydispersity index of 0.245. Zeta potential and electrophoretic mobility were measured as -47.2 and -0.000328 cm2/Vs, respectively thus conferring good stability. FTIR analysis revealed the incidence of extensive hydrogen bonding in its structure and SEM image captured its undulating surface topography. The emollient cream was not susceptible to cracking, creaming or phase separation even after a period of 180 days, when stored at 37° or under low speed centrifugation. Similar results were observed when it was stored at 40°, 4° and -18° for three days and brought to 37° for three cycles. It is concluded that this novel potentially non-toxic neem oil emollient cream can either be used per se or as a base matrix for loading active ingredients and hence function as an efficient delivery system for the same.

A green emollient cream with Hibiscus cannabinus seed oil and an alkyl polyglucoside surfactant has been formulated. It can serve as biological alternatives to synthetic formulations that normally incorporate chemical constituents as surfactants and stabilizers mainly to increase consumer compliance in terms of textural and visual aesthetics. FAME analysis of the oil showed the presence octanoic and decanoic acids. The cream after formulation and ultrasonication, presented a smooth and soft appearance with visual and textural appeal. It showed a mean particle size of 138 nm with a zeta potential of -59.2 mV and an electrophoretic mobility of 0.000459 cm2/Vs. Its SEM image projected well dispersed oil globules in water. FTIR spectrum showed extensive hydrogen bonding. Accelerated stability tests under conditions of freeze thawing, heating cooling and centrifugation revealed no cracking, creaming or phase separation. Similar results were observed during the shelf life studies. It is concluded that this Hibiscus cannabinus cream can be utilized as an emollient base for loading cosmopharmaceutic ingredients for their topical delivery, without any toxicity concerns, as it is formulated from completely natural constituents.