Prospect of herbal medication as prevention against COVID variants.

Personal immunity frolicked an essential role in combating COVID-19 impacts on human health individually and collectively in community. Literature represented the fact about food or nutritional supplements are certified to protect against diseases; this was the reason behind public trust on certain plants and other commercial products to boost up immunity against coronavirus disease. Present study was conducted to observe the attitude of common public towards natural herbs in treating various diseases and to assess the possible potential of herbal medication in prevention of negative impacts of different variants of COVID-19 on human health at herbal clinic named "Pakistan Matab". Results concluded that most of the patients (About 80%) avoided COVID-19 testing even on experiencing major symptoms and they preferred herbal medication. Patients who died by COVID-19 were also experiencing different diseases like liver and Kideny malfunctioning; old age was another significant factor in this case. About 90% of patients were COVID symptomatic and 10% were carrying other diseases during observational study period at herbal clinic. Study represented that patients who visited clinic, have a faith on herbal medication with about 60% of patients in favor of vaccine and allopathic medication in combination with herbal treatment. Study investigated that vaccine was only for one type of variant and use of herbal medicines could be better option to boost up immunity against various COVID variants.

Masitinib analogues with the N-methylpiperazine group replaced - A new hope for the development of anti-COVID-19 drugs.

Masitinib is an orally acceptable tyrosine kinase inhibitor that is currently investigated under clinical trials against cancer, asthma, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. A recent study confirmed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity of masitinib through inhibition of the main protease (Mpro) enzyme, an important pharmacological drug target to block the replication of the coronavirus. However, due to the adverse effects and lower potency of the drug, there are opportunities to design better analogues of masitinib. Herein, we substituted the N-methylpiperazine group of Masitinib with different chemical moieties and evaluated their drug-likeness and toxicities. The filtered analogues were subjected to molecular docking studies which revealed that the analogues with substituents methylamine in M10 (CID10409602), morpholine in M23 (CID59789397) and 4-methylmorpholine in M32 (CID143003625) have a stronger affinity to the drug receptor compared to masitinib. The molecular dynamics (MD) simulation analysis reveals that the identified analogues alter the mobility, structural compactness, accessibility to solvent molecules, and the number of hydrogen bonds in the native target enzyme. These structural alterations can help explain the inhibitory mechanisms of these analogues against the target enzyme. Thus, our studies provide avenues for the design of new masitinib analogues as the SARS-CoV-2 Mpro inhibitors.

Determinants, predictors and negative impacts of burnout among health care workers during COVID-19 pandemic.

The first defense line of the battle, healthcare workers (HCWs), faces a significant challenge in managing the current COVID-19 pandemic. An online electronic survey was sent to HCWs via email and social media networks. Socio-demographic data and work environment-related variables were assessed. Consequences of burnout (BO) were reported, e.g., elicited medical errors. Maslach burnout inventory was used to diagnose BO. Two hundred and eighty-four participants were included with a mean age of 39.83 ± 7.34 years, 70.8% worked in the COVID-19 frontline, 91.9% were followed daily updates about COVID-19, 63.7% were not satisfied with the coordination between triage and isolation, 64.4% got COVID-19 infection, 91.9% had a colleague or family member developed COVID-19 infection, and 21.5% experienced a colleague /a family member died due to COVID-19. Multivariate analysis by linear regression revealed that; working as a frontline HCW (OR 1.28, CI = 0.14-2.55) and sleep deprivation (OR 3.93, CI = 1.88-8.22) were the predictors of burnout.

Vaccine Acceptance and Hesitancy among Hospitalized COVID-19 Patients in Punjab, Pakistan.

Vaccine hesitancy is widespread in many parts of the globe, particularly in low-middle-income countries. Therefore, we surveyed a sample of hospitalized COVID-19 patients to assess COVID-19 vaccine acceptance and vaccine hesitancy in a low-middle-income country. A cross-sectional sample of 385 confirmed reverse transcriptase-polymerase chain reaction COVID-19 patients treated at secondary and tertiary care hospitals in Punjab, Pakistan, were analyzed to assess COVID-19 vaccine uptake and vaccine hesitancy. The construct validity and reliability of the 11-item vaccine hesitancy questionnaire were also examined. In addition, multivariate logistic regression was used. The majority of the COVID-19 patients admitted to hospitals were not vaccinated (84%). Of those who were willing to receive vaccination, the majority (55%) considered vaccines an effective way to protect people from COVID-19. However, those who were not willing to receive their COVID-19 vaccine had significantly higher hesitancy than those willing to receive their COVID-19 vaccine. In addition, older hospitalized COVID-19 patients aged 60 years or above (20-29 years: OR 0.10; 95% CI 0.01-0.72, p = 0.001) and patients from urban areas (OR 3.16 95% CI 1.27-7.87, p = 0.013) were more likely to receive the COVID-19 vaccine than younger patients and patients from rural areas. Patients with no formal education had significantly higher hesitancy (OR 5.26; 96% CI 1.85-14.97, p = 0.002) than participants with graduation and above education. More than half of the study's participants did not trust information shared on social media about COVID-19 vaccines and cited newspapers/news channels as their main source of information. The study provides important insights into COVID-19 vaccine acceptance and the impact of vaccination campaigns. Many unvaccinated COVID-19 patients in hospitals highlight the need for an effective vaccination drive to protect people from acquiring infection and subsequent hospitalization.

Exploring the phytochemicals of Platycodon grandiflorus for TMPRSS2 inhibition in the search for SARS-CoV-2 entry inhibitors.

Platycodon grandiflorus (Jacq.) A. DC. (Campanulaceae) is commonly known as a balloon flower whose rhizomes have been widely utilized in traditional Chinese medicine (TCM) and in various Japanese prescriptions for the treatment of respiratory diseases, diabetes, and inflammatory disorders. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) global pandemic requires priming of the virus's spike (S) protein by cleavage of the S proteins by a multi-domain type II transmembrane serine protease, transmembrane protease serine 2 (TMPRSS2) to gain entry into the host cell. The current research aims at the screening of active phytocompounds of P. grandiflorus as potential inhibitors of cellular TMPRSS2 using molecular docking and molecular dynamics simulations approach. In silico toxicity analyses show that out of a total of 34 phytocompounds selected for the study, 12 compounds obey Lipinski's rule of five and have favourable pharmacokinetic properties. The top three lead molecules identified here were Apigenin, Luteolin and Ferulic acid which exhibited binding energies of -7.47 kcal/mol, -6.8 kcal/mol and -6.62 kcal/mol respectively with corresponding inhibition constants of 3.33 µM, 10.39 µM and 13.95 µM. The complexes between the lead molecules and the receptor were held by hydrogen bond interactions with key residues such as Gly383, Gly385, Glu389, Lys390, Asp435, Ser436, Ser441, Cys465 and Lys467, and hydrophobic interactions with surrounding residues. The stability of the protein-ligand complexes was evaluated during 100 ns molecular dynamics (MD) simulation by analysing key geometric properties such as RMSD, RMSF, radius of gyration, total solvent accessible surface area and the number of hydrogen bonds. The binding free energies analysis using MD simulations revealed that the compounds and TMPRSS2 have favourable thermodynamic interactions, which are primarily driven by van der Waals forces. As a result, the selected bioactive phytochemicals from P. grandiflorus that target the cellular TMPRSS2 could offer an alternative treatment option against SARS-CoV-2 infections.

Potential of antiviral peptide-based SARS-CoV-2 inactivators to combat COVID-19.

The appearance of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of effective antiviral therapeutics for coronavirus disease 2019 (COVID-19), a highly infectious disease caused by the virus, demands the search for alternative therapies. Most antiviral drugs known are passive defenders which must enter the cell to execute their function and suffer from concerns such as permeability and effectiveness, therefore in this current study, we aim to identify peptide inactivators that can act without entering the cells. SARS-CoV-2 spike protein is an essential protein that plays a major role in binding to the host receptor angiotensin-converting enzyme 2 and mediates the viral cell membrane fusion process. SARS vaccines and treatments have also been developed with the spike protein as a target. The virtual screening experiment revealed antiviral peptides which were found to be non-allergen, non-toxic and possess good water solubility. U-1, GST-removed-HR2 and HR2-18 exhibit binding energies of -47.8 kcal/mol, -43.01 kcal/mol, and -40.46 kcal/mol, respectively. The complexes between these peptides and spike protein were stabilized through hydrogen bonds as well as hydrophobic interactions. The stability of the top-ranked peptide with the drug-receptor is evidenced by 50-ns molecular dynamics (MD) simulations. The binding of U-1 induces conformational changes in the spike protein with alterations in its geometric properties such as increased flexibility, decreased compactness, the increased surface area exposed to solvent molecules, and an increase in the number of total hydrogen bonds leading to its probable inactivation. Thus, the identified antiviral peptides can be used as anti-SARS-CoV-2 candidates, inactivating the virus's spike proteins and preventing it from infecting host cells.

The Prospective Effect of Allopurinol on the Oxidative Stress Index and Endothelial Dysfunction in Covid-19.

SARS-CoV-2 by the direct cytopathic effect or indirectly through the propagation of pro-inflammatory cytokines could cause endothelial dysfunction (ED) and oxidative stress (OS). It has been reported that OS is triggered by various types of viral infections, including SARS-CoV-2. Into the bargain, allopurinol is regarded as a potent antioxidant that acts through inhibition of xanthine oxidase (XO), which is an essential enzyme of purine metabolism. Herein, the present study aimed to find the potential protective effects of allopurinol on the biomarkers of OS and ED in patients with severe Covid-19. This single-center cohort study recruited 39 patients with mild-moderate Covid-19 compared with 41 patients with severe Covid-19. Nineteen patients with severe Covid-19 were on the allopurinol treatment because of underlying chronic gout 3 years ago compared with 22 Covid-19 patients not on this treatment. The recruited patients were allocated into three groups: group I, mild-moderate Covid-19 on the standard therapy (n = 39); group II, severe Covid-19 patients on the standard therapy only (n = 22); and group III, severe Covid-19 patients on the standard therapy plus allopurinol (n = 19). The duration of the study was 3 weeks from the time of hospitalization till the time of recovery. In addition, inflammatory biomarkers (D-dimer, LDH, ferritin, CRP, procalcitonin), neutrophil-lymphocyte ratio (NLR), endothelin-1 (ET-1), uric acid and oxidative stress index (OSI), CT scan score, and clinical score were evaluated at the time of admission and discharge regarding the effect of allopurinol treatment adds to the standard treatment of Covid-19. Allopurinol plus standard treatment reduced LDH, ferritin, CRP, procalcitonin, and ET-1 serum level significantly (P < 0.05) compared with Covid-19 patients on standard treatment. Besides, neutrophil (%), lymphocyte (%), and neutrophil-lymphocyte ratio (NLR) were reduced in patients with severe Covid-19 on standard treatment plus allopurinol compared with Covid-19 patients on standard treatment alone (P < 0.01). OSI was higher in patients with severe Covid-19 than mild-moderate Covid-19 patients (P = 0.00001) at admission. At the time of discharge, the oxidative status of Covid-19 patients was significantly improved compared with that at admission (P = 0.01). In conclusion, Covid-19 severity is linked with high OS and inflammatory reaction with ED development. High uric acid in patients with severe Covid-19 is correlated with high OS and inflammatory biomarkers. Allopurinol with standard treatment in patients with severe Covid-19 reduced oxidative and inflammatory disorders with significant amelioration of ED and clinical outcomes.

Opportunistic mycoses in COVID-19 patients/survivors: Epidemic inside a pandemic.

Being considered minor vexations, fungal infections hinder the life of about 15% of the world population superficially, with rare threats to life in case of invasive sepsis. A significant rise in the intrusive mycoses due to machiavellian fungal species is observed over the years due to increased pathology and fatality in people battling life-threatening diseases. Individuals undergoing therapy with immune suppressive drugs plus recovering from viral infections have shown to develop fungal sepsis as secondary infections while recovering or after. Currently, the whole world is fighting against the fright of Coronavirus disease (COVID-19), and corticosteroids being the primitive therapeutic to combat the COVID-19 inflammation, leads to an immune-compromised state, thereby allowing the not so harmful fungi to violate the immune barrier and flourish in the host. A wide range of fungal co-infection is observed in the survivors and patients of COVID-19. Fungal species of Candida, Aspergillus and Mucorales, are burdening the lives of COVID-19 patients/survivors in the form of Yellow/Green, White and Black fungus. This is the first article of its kind to assemble note on fungal infections seen in the current human health scenario till date and provides a strong message to the clinicians, researchers and physicians around the world "non-pathological fungus should not be dismissed as contaminants, they can quell immunocompromised hosts".