No abstract

Today, skin care products and cosmetic preparations containing natural ingredients are widely preferred by consumers. Therefore, many cosmetic brands are encouraged to offer more natural products to the market, such as plant extracts that can be used for their antiaging, antiwrinkle, and depigmentation properties and other cosmetic purposes. In the current study, the volatile constituents of the hexane-soluble fraction of a Stenocarpus sinuatus (family Proteaceae) leaf methanol extract (SSHF) were analyzed using GC/MS analysis. Moreover, the antiaging activity of SSHF was evaluated through in vitro studies of anti-collagenase, anti-elastase, anti-tyrosinase, and anti-hyaluronidase activities. In addition, an in silico docking study was carried out to identify the interaction mechanisms of the major compounds in SSHF with the active sites of the target enzymes. Furthermore, an in silico toxicity study of the identified compounds in SSHF was performed. It was revealed that vitamin E (α-tocopherol) was the major constituent of SSHF, representing 52.59% of the extract, followed by γ-sitosterol (8.65%), neophytadiene (8.19%), β-tocopherol (6.07%), and others. The in vitro studies showed a significant inhibition by SSHF of collagenase, elastase, tyrosinase, and hyaluronidase, with IC50 values of 60.03, 177.5, 67.5, and 38.8 µg/mL, respectively, comparable to those of the positive controls epigallocatechin gallate (ECGC, for collagenase, elastase, hyaluronidase) and kojic acid (for tyrosinase). Additionally, the molecular docking study revealed good acceptable binding scores of the four major compounds, comparable to those of ECGC and kojic acid. Besides, the SSHF identified phytoconstituents showed no predicted potential toxicity nor skin toxicity, as determined in silico. In conclusion, the antiaging potential of SSHF may be attributed to its high content of vitamin E in addition to the synergetic effect of other volatile constituents. Thus, SSHF could be incorporated in pharmaceutical skin care products and cosmetics after further studies.

The novel coronavirus disease COVID-19, caused by the virus SARS CoV-2, has exerted a significant unprecedented economic and medical crisis, in addition to its impact on the daily life and health care systems all over the world. Regrettably, no vaccines or drugs are currently available for this new critical emerging human disease. Joining the global fight against COVID-19, in this study we aim at identifying a potential novel inhibitor for SARS COV-2 2 0-O-methyltransferase (nsp16) which is one of the most attractive targets in the virus life cycle, responsible for the viral RNA protection via a cap formation process. Firstly, nsp16 enzyme bound to Sinefungin was retrieved from the protein data bank (PDB ID: 6WKQ), then, a 3D pharmacophore model was constructed to be applied to screen 48 Million drug-like compounds of the Zinc database. This resulted in only 24 compounds which were subsequently docked into the enzyme. The best four score-ordered hits from the docking outcome exhibited better scores compared to Sinefungin. Finally, three molecular dynamics (MD) simulation experiments for 150 ns were carried out as a refinement step for our proposed approach. The MD and MM-PBSA outputs revealed compound 11 as the best potential nsp16 inhibitor herein identified, as it displayed a better stability and average binding free energy for the ligand-enzyme complex compared to Sinefungin.

In continuation of our antecedent work against COVID-19, three natural compounds, namely, Luteoside C (130), Kahalalide E (184), and Streptovaricin B (278) were determined as the most promising SARS-CoV-2 main protease (Mpro) inhibitors among 310 naturally originated antiviral compounds. This was performed via a multi-step in silico method. At first, a molecular structure similarity study was done with PRD_002214, the co-crystallized ligand of Mpro (PDB ID: 6LU7), and favored thirty compounds. Subsequently, the fingerprint study performed with respect to PRD_002214 resulted in the election of sixteen compounds (7, 128, 130, 156, 157, 158, 180, 184, 203, 204, 210, 237, 264, 276, 277, and 278). Then, results of molecular docking versus Mpro PDB ID: 6LU7 favored eight compounds (128, 130, 156, 180, 184, 203, 204, and 278) based on their binding affinities. Then, in silico toxicity studies were performed for the promising compounds and revealed that all of them have good toxicity profiles. Finally, molecular dynamic (MD) simulation experiments were carried out for compounds 130, 184, and 278, which exhibited the best binding modes against Mpro. MD tests revealed that luteoside C (130) has the greatest potential to inhibit SARS-CoV-2 main protease.

The world has recently been struck by the SARS-Cov-2 pandemic, a situation that people have never before experienced. Infections are increasing without reaching a peak. The WHO has reported more than 25 million infections and nearly 857,766 confirmed deaths. Safety measures are insufficient and there are still no approved drugs for the COVID-19 disease. Thus, it is an urgent necessity to develop a specific inhibitor for COVID-19. One of the most attractive targets in the virus life cycle is the polymerase enzyme responsible for the replication of the virus genome. Here, we describe our Structure-Based Drug Design (SBDD) protocol for designing of a new potential inhibitor for SARS-COV-2 RNA-dependent RNA Polymerase. Firstly, the crystal structure of the enzyme was retrieved from the protein data bank PDB ID (7bv2). Then, Fragment-Based Drug Design (FBDD) strategy was implemented using Discovery Studio 2016. The five best generated fragments were linked together using suitable carbon linkers to yield compound MAW-22. Thereafter, the strength of the binds between compound MAW-22 and the SARS-COV-2 RNA-dependent RNA Polymerase was predicted by docking strategy using docking software. MAW-22 achieved a high docking score, even more so than the score achieved by Remdesivir, indicating very strong binding between MAW-22 and its target. Finally, three molecular dynamic simulation experiments were performed for 150 ns to validate our concept of design. The three experiments revealed that MAW-22 has a great potentiality to inhibit the SARS-COV-2 RNA-dependent RNA Polymerase compared to Remdesivir. Also, it is thought that this study has proven SBDD to be the most suitable avenue for future drug development for the COVID-19 infection.