Mechanistic insight of Staphylococcus aureus associated skin cancer in humans by Santalum album derived phytochemicals: an extensive computational and experimental approaches.

An excessive amount of multidrug-resistant Staphylococcus aureus is commonly associated with actinic keratosis (AK) and squamous cell carcinoma (SCC) by secreted virulence products that induced the chronic inflammation leading to skin cancer which is regulated by staphylococcal accessory regulator (SarA). It is worth noting that there is currently no existing published study that reports on the inhibitory activity of phytochemicals derived from Santalum album on the SarA protein through in silico approach. Therefore, our study has been designed to find the potential inhibitors of S. aureus SarA protein from S. album-derived phytochemicals. The molecular docking study was performed targeting the SarA protein of S. aureus, and CID:5280441, CID:162350, and CID: 5281675 compounds showed the highest binding energy with -9.4 kcal/mol, -9.0 kcal/mol, and -8.6 kcal/mol respectively. Further, molecular dynamics simulation revealed that the docked complexes were relatively stable during the 100 ns simulation period whereas the MMPBSA binding free energy proposed that the ligands were sustained with their binding site. All three complexes were found to be similar in distribution with the apoprotein through PCA analysis indicating conformational stability throughout the MD simulation. Moreover, all three compounds' ADMET profiles revealed positive results, and the AMES test did not show any toxicity whereas the pharmacophore study also indicates a closer match between the pharmacophore model and the compounds. After comprehensive in silico studies we evolved three best compounds, namely, Vitexin, Isovitexin, and Orientin, which were conducted in vitro assay for further confirmation of their inhibitory activity and results exhibited all of these compounds showed strong inhibitory activity against S. aureus. The overall result suggests that these compounds could be used as a natural lead to inhibit the pathogenesis of S. aureus and antibiotic therapy for S. aureus-associated skin cancer in humans as well.

Biochemical and molecular docking-based strategies of Acalypha indica and Boerhavia diffusa extract by targeting bacterial strains and cancer proteins.

Antibiotic-resistant microbes have emerged around the world, presenting a risk to health. Plant-derived drugs have become a potential source for the production of antibiotic-resistant drugs and cancer therapies. In this study, we investigated the antibacterial, cytotoxic and antioxidant properties of Acalypha indica and Boerhavia diffusa, and conducted in silico molecular docking experiments against EGFR and VEGFR-2 proteins. The metabolic extract of A. indica inhibited Streptococcus iniae and Staphylococcus sciuri with inhibition zones of 21.66 ± 0.57 mm and 20.33 ± 0.57 mm, respectively. The B. diffusa leaf extract produced inhibition zones of 20.3333 ± 0.5773 mm and 20.33 ± 0.57 mm against Streptococcus iniae and Edwardsiella anguillarum, respectively. A. indica and B. diffusa extracts had toxicities of 162.01 µg/ml and 175.6 µg/ml, respectively. Moreover, B. diffusa (IC50 =154.42 µg/ml) leaf extract exhibited moderately higher antioxidant activity compared with the A. indica (IC50 = 218.97 µg/ml) leaf extract. Multiple interactions were observed at Leu694, Met769 and Leu820 sites for EGFR and at Asp1046 and Cys1045 sites for VEGFR during the molecular docking study. CID-235030, CID-70825 and CID-156619353 had binding energies of -7.6 kJ/mol, -7.5 kJ/mol and -7.6 kJ/mol, respectively, with EGFR protein. VEGFR-2 protein had docking energies of -7.5 kJ/mol, -7.6 kJ/mol and -7.3 kJ/mol, respectively, for CID-6420353, CID-156619353 and CID-70825 compounds. The MD simulation trajectories revealed the hit compound; CID-235030 and EGFR complex, CID-6420353 and VEGFR-2 exhibit stable profile in the root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bond and root mean square fluctuation (RMSF) and the binding free energy by MM-PBSA method. This study indicates that methanol extracts of A. indica and B. diffusa may play a crucial role in developing antibiotic-resistant and cancer drugs.Communicated by Ramaswamy H. Sarma.

Clinical manifestations and socio-demographic status of COVID-19 patients during the second-wave of pandemic: A Bangladeshi experience.

BACKGROUND: Bangladesh is a densely populated country with a substandard healthcare system and a mediocre economic framework. Due to the enormous number of people who have been unaware until now, the development of COVID-19's second-wave infection has become a severe threat. The present investigation aimed to characterize the clinical and socio-demographic characteristics of COVID-19 in Bangladesh. METHODS: A cross-sectional analysis was carried out from all the other COVID-19 patients and confirmed by RT-PCR undergoing a specialized COVID-19 hospital. From March 1 to April 15, 2021, a total of 1326 samples were collected. Samples were only obtained from non-critical COVID-19 patients as critically ill patients required emergency intensive care medications. Then, from April 17 to May 03, 2021, SARS-CoV-2 infection and clinical assessment was performed based on interim guidelines from the WHO. The diagnosis was conducted through RT-PCR. Later, identifying the symptomatic and asymptomatic patient based on checking the Clinical Observation Form (COF). The patients filled the COF form. Finally, statistical analyses were done using the SPSS 20 statistical program. RESULTS: In this investigation, a total of 326 patients were diagnosed as COVID-19 positive. Among them, approximately 19.02% (n = 62) were asymptomatic, and 80.98% (n = 264) were symptomatic. Here, the finding shows that the occurrence of this infection was varied depending on age, sex, residence, occupation, smoking habit, comorbidities, etc. However, Males (60.12%) were more affected than females (39.88%), and, surprisingly, this pandemic infected both urban and rural residents almost equally (urban = 50.92%; rural = 49.08%). Approximately 19% of the asymptomatic and 62% of symptomatic cases had at least one comorbid disorder. Interestingly, an unexpected result was exhibited in the case of smokers, where non-smokers were more affected than smokers. The study indicates community transmission of COVID 19, where people were highly infected at their occupations (35.58%), at houses (23.93%) and by traveling (12.88%). Noteworthy, according to this report, a large number (19.33%) of individuals did not know exactly how they were contaminated with SARS-CoV-2. Patients were most commonly treated by an antibiotic 95.09%, followed in second by corticosteroid 46.01%. Anti-viral drugs, remdesivir, and oxygenation are also needed for other patients. Among those, who were being treated, approximately 69.33% were isolated at home, 27.91% were being treated at dedicated COVID-19 hospitals. Finally, 96.63% were discharged without complications, and 0.03% has died. CONCLUSION: This investigation concludes that males became more infected than females. Interestingly, both urban and rural people became nearly equally infected. It noticed community transmission of SARS-CoV-2, where people were highly infected at their workplaces. A higher rate of silent transmission indicates that more caution is needed to identify asymptomatic patients. Most of the infected people were isolated at home whereas nearly one-fourth were treated at hospitals. Clinically, antibiotics were the most widely used treatment. However, the majority of the patients were discharged without complications. The current investigation would be helpful to understand the clinical manifestations and socio-demographic situations during the second wave of the COVID-19 pandemic in Bangladesh.

Computational discovery of plant-based inhibitors against human carbonic anhydrase IX and molecular dynamics simulation.

Carbonic anhydrase IX (hCAIX) is a membrane-spanning metalloenzyme, encoded by CA9 gene, which can lead to various carcinomas if upregulated. Due to its overexpression in many cancer tissues, hCAIX has become a promising target for developing anticancer therapeutics. Furthermore, several classes of small-molecules have shown to inhibit the hCAIX expression. In this study, therefore, we screened (n = 42) plant-derived compounds to identify the most potent hCAIX inhibitors and to understand their interactions with hCAIX and drug candidacy through in silico approaches. Among all, only three compounds (i.e. fraxoside, scopolin, and xanthone,) provided higher binding affinity toward hCAIX protein as compared to the native ligand. In standard docking, scopolin showed -4.97 kcal/mol of binding energy with hCAIX while control ligand provided -4.45 kcal/mol. In precise docking, the highest binding affinity was found for fraxoside (-7.67 kcal/mol) as compared to -3.04 kcal/mol of the control. The Gibbs free energy (ΔG) of these potent leads was also consistent and in support of the docking studies. The binding interactions were also found to be stable in dynamics simulation. Furthermore, analysis of protein-protein interactions and co-expression revealed the possible association of CA9 gene with other tumorous genes, especially angiogenesis factor HIF1A which will most likely be affected by the identified inhibitors. With further experimental validation, therefore, these potential inhibitors could be effective against hCAIX protein, thereby, paving the way for prospective anticancer therapeutics.Communicated by Ramaswamy H. Sarma.