RESUMEN
The Dengue virus (DENV) has been increasingly recognized as a prevalent viral pathogen responsible for global transmission of infection. It has been established that DENV's NS5 methyltransferase (MTase) controls viral replication. As a result, NS5 MTase is considered a potentially useful drug target for DENV. In this study, the two phases of virtual screening were conducted using the ML-based QSAR model and molecular docking to identify potential compounds against NS5 of DENV. Four medicinal plants [Aloe vera, Cannabis sativa (Hemp), Ocimum sanctum (Holy Basil; Tulsi), and Zingiber officinale (Ginger)] that showed anti-viral properties were selected for sourcing the phytochemicals and screening them against NS5. Additionally, re-docking at higher exhaustiveness and interaction analysis were performed which resulted in the identification of the top four hits (135398658, 5281675, 119394, and 969516) which showed comparable results with the control Sinefungin (SFG). Post molecular dynamics simulation, 135398658 showed the lowest RMSD (0.4-0.5 nm) and the maximum number of hydrogen bonds (eight hydrogen bonds) after the control while 5281675 and 969516 showed comparable hydrogen bonds to the control. These compounds showed direct interactions with the catalytic site residues GLU111 and ASP131, in addition to this these compounds showed stable complex formation as depicted by principal component analysis and free energy landscape. 135398658 showed lower total binding free energy (ΔGTotal = -36.56 kcal/mol) than the control, while 5281675 had comparable values to the control (ΔGTotal = -34.1 kcal/mol). Overall, the purpose of this study was to identify phytochemicals that inhibit NS5 function, that could be further tested experimentally to treat dengue virus (DENV).Communicated by Ramaswamy H. Sarma.
RESUMEN
Recently, we reported high antibacterial efficiency of Loranthus acaciae (LA) against different standard strains of bacteria including Methicillin-Resistant Staphylococcus aureus (MRSA). Therefore, this study aimed to confirm the effectiveness of LA against clinically isolated Staphylococcus aureus (SA) including ß-lactamase producer (Blac) and MRSA. Forty-eight SA isolates collected from various clinical samples were used in this study. Antibiotics susceptibility profile was determined for twenty different antibiotics using automated Microscan Walkaway 96 Plus system as recommended by Clinical and Laboratory Standards Institute (CLSI) guidelines. This system also identified ß-lactamase producers and MRSA. In the meantime, LA ethanolic extract was fractionated using liquid-liquid fraction method to hexane, dichloromethane DCM and methanol 80% fractions. Antimicrobial activities of LA extract and fraction were performed with agar well diffusion method for all SA isolates, MIC and MBC were also recorded. Phytochemical screening for various phyto-constituent classes of LA ethanolic extract was determined. Out of 48 SA isolates, Cefoxitin-positive MRSA represent 31 (64.6%), Blac 17 (35.4%), and 41 (85.4%) were multidrug-resistant SA, which was resistant at least to one antibiotic from three different categories. All isolates were resistant to ampicillin and penicillin. Antimicrobial activities of LA extract and fractions revealed that ethanol extract was active against all isolated SA with inhibition zone ranged from 33 ± 2.00 to 25 ± 3.05 mm. While DCM exhibited the largest inhibition zone range from 37 ± 3.00 to 33 ± 2.00 mm. This study is first of its kind conforming the high antibacterial activity of LA against SA isolated from a different source of infection. The study concluded that LA extract and fractions are active and give positive result for all isolated SA. Therefore, suitable pharmacological formulation of LA extract as a promising antibacterial agent for the treatment of SA infection should be given extreme priority.
RESUMEN
The emergence of drug-resistant organisms have been increasing globally; therefore, it is a burning need to find an alternative drug to get rid of the diseases caused by resistant strains. This study aims to evaluate the antimicrobial and wound healing activities of Loranthus acacia, Cassia obtusifolia and Cymbopogon proximus plants. All the plants were collected and extracted - by maceration method. Antimicrobial activities determined using standard ATCC strain for Gram-positive bacteria (Bacillus subtilis, Bacillus crew, Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus) and Gram-negative bacteria (Shigella sonnnei, Salmonella Typhimurium, Salmonella typhi, Klebsiella pnuemoniae, Escherichia coli and Pseudomonas aeruginosa) following agar well diffusion method. Plants extracts were prepared as gel and investigated for in vivo wound healing activities in rats. Histological studies were performed on animals' skin. The results showed that all tested plants have various antimicrobial and wound healing activities. Out of these plants, L. acacia exhibited the best result; it revealed a significant result for antimicrobial activities counter to all Gram-positive, Gram-negative bacteria and wound healing activities in comparing with the reference drug. Thus, it is essential to consider L. acacia as a prospective source in progress in the synthesis of a new antimicrobial drug for the treatment of infectious diseases.