Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin’s in silico interaction with protein tyrosine phosphate 1B, as well as it’s in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule’s module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same.

Chromium is a toxic heavy metal abundantly present in the environment, specifically in groundwater. The groundwater in Saudi Arabia was assessed for heavy metal presence; chromium was detected at a high concentration in Madinah. Many researchers have used various bioprocesses over the last few decades to mitigate Cr(VI) toxicity. The genus Pseudomonas member Pseudomonas putida is widely dispersed in the natural environment. P. putida is chromate-resistant and has a high chromate reduction rate. Bioremediation procedures can eradicate the most potently toxic metal, Cr(VI), in water, air, and soil. Chromate reductase (ChrR) is a bacterial enzyme from P. putida that can be utilized in bioremediation to remove chromate from the environment in a cost-effective and environmentally safe approach. To comprehend the role of ChrR in reducing Cr(VI) to Cr(III), a thorough sequence analysis was followed by constructing models for wild-type and mutants by applying several homology modeling techniques. The protein structure quality of the generated models was evaluated, and the best model was adopted for further optimization by employing an energy minimization technique. Molecular docking studies investigated the intra-molecular interaction between wild-type and mutant ChrR and Cr(VI). Our study is a novel method for determining the 3D structure and interaction of ChrR with Cr(VI) to convert it to a less hazardous form (III). Additionally, it provides stable mutants: Arg83Trp, Gly124Ile, and His127Trp, with a high binding affinity for Cr(VI), which can be considered for protein engineering to produce stable and efficacious enzymes to reduce Cr(VI) to a less toxic form.

Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of −9.95, −8.92, and −8.71 kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (−6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

Microorganisms are ubiquitously present in the environment and exert significant influence on numerous natural phenomena. The soil and groundwater systems, precipitation, and effluent outfalls from factories, refineries, and waste treatment facilities are all sources of heavy metal contamination. For example, Madinah, Saudi Arabia, has alarmingly high levels of lead and cadmium. The non-essential minerals cadmium (Cd) and lead (Pb) have been linked to damage to vital organs. Bioremediation is an essential component in the process of cleaning up polluted soil and water where biological agents such as bacteria are used to remove the contaminants. It is demonstrated that Pseudomonas aeruginosa (P. aeruginosa) isolated from activated sludge was able to remove Cd and Pb from water. The protein sequence of metallothionein from P. aeruginosa was retrieved to explore it for physicoparameters, orthologs, domain, family, motifs, and conserved residues. The homology structure was generated, and models were validated. Docking of the best model with the heavy metals was carried out to inspect the intramolecular interactions. The target protein was found to belong to the “metallothionein_pro” family, containing six motifs, and showed a close orthologous relationship with other heavy metal-resistant bacteria. The best model was generated by Phyre2. In this study, three key residues of metallothionein were identified that participate in heavy metal (Pb and Cd) binding, viz., Ala33, Ser34, and Glu59. In addition, the study provides an essential basis to explore protein engineering for the optimum use of metallothionein protein to reduce/remove heavy metals from the environment.