Genomic epidemiology of SARS-CoV-2 is imperative to explore the transmission, evolution, and also pathogenicity of viruses. The emergence of SARS-CoV-2 variants of concern posed a severe threat to the global public health efforts. To assess the potential consequence of these emerging variants on public health, continuous molecular epidemiology is of vital importance. The current study has been designed to investigate the major SARS-CoV-2 variants and emerging mutations in virus structural and non-structural proteins (NSP) during the fourth wave in September 2021 from the Punjab province of Pakistan. Twenty SARS-CoV-2 positive samples have been collected from major cities were subjected to next-generation sequencing. Among the 20 whole genomes (GenBank Accession SRR16294858-SRR16294877), 2 samples failed to be completely sequenced. These genome sequences harbored 207 non-synonymous mutations, among which 19 were unique to GISAID. The genome sequences were detected: Delta 21I, 21J variants (B.1.617.2). Mutation’s spike_F157del, spike_P681R, spike_T478K, spike_T19R, spike_L452R, spike_D614G, spike_G142D, spike_E156G, and spike_R158del have been detected in all samples where K1086Q, E554K, and C1250W were unique in spike protein. These genomic sequences also harbored 129 non-synonymous mutations in NSP. The most common were NSP3_P1469S (N = 17), NSP3_A488S (N = 17), NSP3_P1228L (N = 17), NSP4_V167L (N = 17), NSP4_T492I (N = 17), NSP6_T77A (N = 17), NSP14_A394V (N = 17), NSP12_G671S (N = 18), and NSP13_P77L (N = 18). The mutation, F313Y in NSP12, detected in the current study, was found in a single isolate from Belgium. Numerous other unique mutations have been detected in the virus papain-like protease (NSP3), main protease (NSP5), and RNA-dependent RNA polymerase (NSP12). The most common non-synonymous mutations in the spike protein were subjected to stability analysis, exhibiting a stabilizing effect on structures. The presence of Delta variants may affect therapeutic efforts and vaccine efficacy. Continuous genomic epidemiology of SARS-CoV-2 in Pakistan may be useful for better management of SARS-CoV-2 infections.

Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self‐tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti‐inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN‐γ), interleukin 3 (IL‐3), and tumor necrosis factor alpha (TNF‐α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein‐ligand docking and peptide‐protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S‐score of ‐11.3018 and HADDOCK score of −10.3 ± 2.5 kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN‐γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN‐γ, IL‐3, and TNF‐α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN‐γ with S‐scores of ‐10.98 and ‐10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL‐3 with S‐scores of ‐8.81, ‐8.64, and ‐8.17, respectively.

Cardiovascular diseases (CVD), primarily inflammatory cardiomyopathy, are characterized by the infiltration of inflammatory cells into the myocardium. It has a relatively high risk of deteriorating heart function and has heterogeneous etiologies. Inflammatory cardiomyopathy is mainly mediated by viral infections but can also be mediated by protozoa, fungal or bacterial infections. Besides that, there are a wide variety of drugs, toxic substances, and systemic immune-mediated diseases that result in the development of cardiovascular diseases (CVDs). Despite broad research, inflammatory cardiomyopathy has a poor prognosis. The roles of the pathogens, host genomic counterparts and environmental triggers in the progression of disease are still under consideration, including the role of some viruses as active inducers and others as bystanders. In this review article, we review the available evidence on the types, pathogenesis and treatment of myocarditis, inflammatory cardiomyopathy, and atherosclerosis with a particular focus on virus-associated cardiac diseases.

Introduction: Arsenic trioxide (As₂O₃) is an environmental contaminant that may cause hepatic injuries. As₂O₃-induced liver injuries are detected as an underlying cause of hepatocellular carcinoma (HCC) around the globe. The present study aimed to investigate the potential of Gardenia latifolia (GL) extracts against oxidative stress and apoptotic activity in HCC-induced rats and to explore in silico molecular docking analysis of phytocompounds of G. latifolia.Methods: The present study was designed to investigate the hepato-protective effect of ethanol and n-hexane extract of G. latifolia. Phytochemical analysis was performed using gas-chromatography-mass spectrometry (GC-MS), and the identified metabolites were used for computational docking analysis. The binding potential and inhibitory effect of the identified metabolites against inflammatory markers were assessed. Fifty male albino rats were selected for the in vivo study and were randomly divided into five groups, with 10 rats in each group. Group I is the control group. Hepatotoxicity was induced in groups II, III, IV, and V with 350 mg/kg/day of As₂O₃. Group II was taken as positive control, Group III and IV were treated with ethanol and n-hexane extract of G. latifolia, respectively, and Group V was treated with cisplatin 3.0 mg/kg/day. At the end of treatment, different stress and liver biomarkers were also analyzed.Results and Discussion: The quantitative phytochemical profiling revealed a high content of total flavonoid and tannins found at 5.731 ± 0.1856 mg quercetin equivalent (QE)/g and 86.31 ± 14.20 mg tannic acid equivalent (TAE)/g in G. latifolia n-hexane extract, while a significant concentration of TFC was 276.821 ± 2.19 mg gallic acid equivalent (GAE)/g, in ethanolic extract. GC-MS analysis resulted in the identification of 26 metabolites in ethanol extract while 32 metabolites in n-hexane extract, respectively. Both the extracts restored the abnormal levels of stress markers (p < 0.05) in Groups III and IV, and were comparable to the comparative control group V, which was given cisplatin as the standard drug. The histopathological examination revealed the regeneration of hepatocytes, dilated sinusoidal cells, necrosis, and distorted hepatic architecture observed in arsenic trioxide hepatotoxic liver. Among the top most identified metabolites from GC-MS analysis, stigmasterol exhibited −8.3 and −7.1 kcal/mol in silico binding affinities against cyclooxygenase-2 (COX-2), and interleukin (IL-6), respectively, while Dasycarpidan-1-methanol exhibited the best binding affinities of −6.8 and −7.2 kcal/mole against matrixmetalloprotinease (MMP)-3 and heat shock protein-90 (HSP-90), respectively. 6-AH-cAMP showed the best docking score of −7.5 kcal/mol for the vascular endothelial growth factor (VEGF) macromolecule. Metabolite Dasycarpidan-1-methanol, acetate represented drug like properties so it was further analyzed by MD simulation and stable dynamic nature of protein ligand complex was evaluated.Conclusion: In conclusion, the effective therapeutic potential of G. latifolia extracts targeted oxidative stress, increasing antioxidant activities and inhibiting inflammation and liver complications at early stages. Further research on the molecular level may further explore the anticancer potential of this plant against various types of cancers.

Nanotechnology has revolutionized the drug delivery approaches to improve the existing issues of conventional drug delivery systems, especially, the green synthesis of nanoparticles is becoming more suitable for different activities. In this study, phyto-fabricated gold nanoparticles (GNPs) were synthesized using Zanthoxylum armatum aqueous extract. GNPs were characterized by different techniques using UV-Vis absorption spectroscopy, X-Ray diffraction (XRD), Fourier transformation infrared spectroscopy (FTIR), Dynamic light scattering (DLS), and scanning electron microscopy (SEM). UV-Vis spectroscopy showed peak at 550 nm. XRD confirmed the crystalline nature of nanoparticles. FTIR showed presence of different functional groups such as C–O, N–H, C═O, C–H, and O–H. SEM and DLS have shown particle size of 30 nm. The antibacterial activity of plant extract and green synthesized GNP were tested against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella pneumonia which revealed remarkable inhibition of these microorganisms. Burn wound was created on 16 rats and randomized into four groups. Group I was untreated. Group II rats were treated by applying topical ointment cream. Group III rats were treated by applying Zanthoxylum armatum cream, and group IV rats were treated by applying GNPs-based cream. Treatment was carried out for 14 days. Wounds treated with GNPs-based cream decreased consistently and almost completely. It can be concluded that GNPs-based cream can be used as an ointment to treat wounds especially burn wounds.