ABSTRACT
SARS-CoV-2 triggered a worldwide medical crisis, affecting the world's social, emotional, physical, and economic equilibrium. However, treatment choices and targets for finding a solution to COVID-19's threat are becoming limited. A viable approach to combating the threat of COVID-19 is by unraveling newer pharmacological and therapeutic targets pertinent in the viral survival and adaptive mechanisms within the host biological milieu which in turn provides the opportunity to discover promising inhibitors against COVID-19. Therefore, using high-throughput virtual screening, manually curated compounds library from some medicinal plants were screened against four main drivers of SARS-CoV-2 (spike glycoprotein, PLpro, 3CLpro, and RdRp). In addition, molecular docking, Prime MM/GBSA (molecular mechanics/generalized Born surface area) analysis, molecular dynamics (MD) simulation, and drug-likeness screening were performed to identify potential phytodrugs candidates for COVID-19 treatment. In support of these approaches, we used a series of computational modeling approaches to develop therapeutic agents against COVID-19. Out of the screened compounds against the selected SARS-CoV-2 therapeutic targets, only compounds with no violations of Lipinski's rule of five and high binding affinity were considered as potential anti-COVID-19 drugs. However, lonchocarpol A, diplacol, and broussonol E (lead compounds) were recorded as the best compounds that satisfied this requirement, and they demonstrated their highest binding affinity against 3CLpro. Therefore, the 3CLpro target and the three lead compounds were selected for further analysis. Through protein-ligand mapping and interaction profiling, the three lead compounds formed essential interactions such as hydrogen bonds and hydrophobic interactions with amino acid residues at the binding pocket of 3CLpro. The key amino acid residues at the 3CLpro active site participating in the hydrophobic and polar inter/intra molecular interaction were TYR54, PRO52, CYS44, MET49, MET165, CYS145, HIS41, THR26, THR25, GLN189, and THR190. The compounds demonstrated stable protein-ligand complexes in the active site of the target (3CLpro) over a 100 ns simulation period with stable protein-ligand trajectories. Drug-likeness screening shows that the compounds are druggable molecules, and the toxicity descriptors established that the compounds demonstrated a good biosafety profile. Furthermore, the compounds were chemically reactive with promising molecular electron potential properties. Collectively, we propose that the discovered lead compounds may open the way for establishing phytodrugs to manage COVID-19 pandemics and new chemical libraries to prevent COVID-19 entry into the host based on the findings of this computational investigation.
ABSTRACT
Breast cancer has consistently been a global challenge that is prevalent among women. There is a continuous increase in the high number of women mortality rates because of breast cancer and affecting nations at all modernization levels. Women with high-risk factors, including hereditary, obesity, and menopause, have the possibility of developing breast cancer growth. With the advent of radiotherapy, chemotherapy, hormone therapy, and surgery in breast cancer treatment, breast cancer survivors have increased. Also, the design and development of drugs targeting therapeutic enzymes effectively treat the tumour cells early. However, long-term use of anticancer drugs has been linked to severe side effects. This research aims to develop potential drug candidates from Moringa oleifera, which could serve as anticancer agents. In silico analysis using Schrödinger Molecular Drug Discovery Suite and SWISS ADME was employed to determine the therapeutic potential of phytochemicals from M oleifera against breast cancer via molecular docking, pharmacokinetic parameters, and drug-like properties. The result shows that rutin, vicenin-2, and quercetin-3-O-glucoside have the highest binding energy of -7.522, -6.808, and -6.635 kcal/mol, respectively, in the active site of BRCA-1. The essential amino acids involved in the protein-ligand interaction following active site analysis are ASN 1678, ASN 1774, GLY 1656, LEU 1657, GLN 1779, LYS 1702, SER 1655, PHE 1662, ARG 1699, GLU 1698, and VAL 1654. Thus, we propose that bioactive compounds from M oleifera may be potential novel drug candidates in the treatment of breast cancer.
ABSTRACT
The chemistry of Cassia siamea L., C. occidentalis L. (Fabaceae), Cnestis ferruginea Vahl ex DC (Connaraceae), Anthocleista djalonensis A. Chev (Loganiaceae), Solanum torvum Swartz and S. erianthum G. Don (Solanaceae) volatiles grown in Nigeria have been studied. The essential oils were obtained by hydrodistillation and analyzed by GC and GC-MS. The main compounds of C. siamea were (E)-geranyl acetone (5.8%), 1-octen-3-ol (5.8%), linalool (7.8%), iso-italicene (15.4%) and (E)-beta-damascenone (11.0%). On the other hand, C. occidentalis consisted mainly of (E)-geranyl acetone (8.0%), hexahydrofarnesylacetone (24.0%) and (E)-phytol acetate (40.7%). The oil of C. ferruginea was comprised mainly of (E)-geranyl acetone (13.7%), (E)-alpha-ionone (9.5%), phytol (5.8%), pentadecanal (6.1%) and 1-octen-3-ol (5.5%). The main compounds of A. djalonensis were alpha-humulene (31.9%), beta-caryophyllene (17.8%), humulene epoxide II (12.7%) and caryophyllene oxide (5.9%). The main volatiles of S. torvum were (E)-phytol acetate (38.7%), pentadecanal (25.3%) and (E)-geranyl acetone (5.0%). Apart from methyl salicylate (4.5%), tetradecanal (2.2%), 2-pentyl furan (1.8%), hexahydrofarnesylacetone (1.6%) and hexadecanal (1.1%), all other compounds were either present in trace quantity or in amounts less than 1%. On the other hand, alpha-humulene (46.6%) and beta-caryophyllene (20.6%) were the compounds occurring in higher quantities in S. erianthum. The volatile oil contents of Cassia siamea, Cnestis ferruginea, Anthocleista djalonensis and Solanum torvum are being reported for the first time.
