The relationship between hand hygiene and rates of acute respiratory infections among Umrah pilgrims: A pilot randomised controlled trial.

BACKGROUND: There is a lack of randomised controlled trials (RCTs) investigating the role of hand hygiene in preventing and containing acute respiratory infections (ARIs) in mass gatherings. In this pilot RCT, we assessed the feasibility of establishing a large-scale trial to explore the relationship between practising hand hygiene and rates of ARI in Umrah pilgrimage amidst the COVID-19 pandemic. METHODS: A parallel RCT was conducted in hotels in Makkah, Saudi Arabia, between April and July 2021. Domestic adult pilgrims who consented to participate were randomised 1:1 to the intervention group who received alcohol-based hand rub (ABHR) and instructions, or to the control group who did not receive ABHR or instructions but were free to use their own supplies. Pilgrims in both groups were then followed up for seven days for ARI symptoms. The primary outcome was the difference in the proportions of syndromic ARIs among pilgrims between the randomised groups. RESULTS: A total of 507 (control: intervention = 267: 240) participants aged between 18 and 75 (median 34) years were randomised; 61 participants were lost to follow-up or withdrew leaving 446 participants (control: intervention = 237:209) for the primary outcome analysis; of whom 10 (2.2 %) had developed at least one respiratory symptom, three (0.7 %) had 'possible ILI' and two (0.4 %) had 'possible COVID-19'. The analysis of the primary outcome found no evidence of difference in the proportions of ARIs between the randomised groups (odds ratio 1.1 [0.3-4.0] for intervention relative to control). CONCLUSION: This pilot trial suggests that conducting a future definitive RCT to assess the role of hand hygiene in the prevention of ARIs is feasible in Umrah setting amidst such a pandemic; however, outcomes from this trial are inconclusive, and such a study would need to be very large given the low rates of outcomes observed here. TRIAL REGISTRATION: This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12622001287729), the full protocol can be accessed there.

Network Pharmacology Approach for Medicinal Plants: Review and Assessment.

Natural products have played a critical role in medicine due to their ability to bind and modulate cellular targets involved in disease. Medicinal plants hold a variety of bioactive scaffolds for the treatment of multiple disorders. The less adverse effects, affordability, and easy accessibility highlight their potential in traditional remedies. Identifying pharmacological targets from active ingredients of medicinal plants has become a hot topic for biomedical research to generate innovative therapies. By developing an unprecedented opportunity for the systematic investigation of traditional medicines, network pharmacology is evolving as a systematic paradigm and becoming a frontier research field of drug discovery and development. The advancement of network pharmacology has opened up new avenues for understanding the complex bioactive components found in various medicinal plants. This study is attributed to a comprehensive summary of network pharmacology based on current research, highlighting various active ingredients, related techniques/tools/databases, and drug discovery and development applications. Moreover, this study would serve as a protocol for discovering novel compounds to explore the full range of biological potential of traditionally used plants. We have attempted to cover this vast topic in the review form. We hope it will serve as a significant pioneer for researchers working with medicinal plants by employing network pharmacology approaches.

Syndromic surveillance of respiratory-tract infections and hand hygiene practice among pilgrims attended Hajj in 2021: a cohort study.

BACKGROUND: The risk of transmission of viral respiratory tract infections (RTIs) is high in mass gatherings including Hajj. This cohort study estimated the incidence of symptomatic RTIs and hand hygiene compliance with its impact among Hajj pilgrims during the COVID-19 pandemic. METHODS: During the week of Hajj rituals in 2021, domestic pilgrims were recruited by phone and asked to complete a baseline questionnaire. Pilgrims were followed up after seven days using a questionnaire about the development of symptoms, and practices of hand hygiene. Syndromic definitions were used to clinically diagnose 'possible' influenza-like illnesses (ILI) and COVID-19 infection. RESULTS: A total of 510 pilgrims aged between 18 and 69 (median of 50) years completed the questionnaire, 280 (54.9%) of whom were female, and all of them (except for one) were vaccinated against COVID-19 with at least one dose. The mean (± SD) of pilgrims' hand hygiene knowledge score (on a scale of 0 to 6) was 4.15 (± 1.22), and a higher level of knowledge was correlated with a higher frequency of handwashing using soap and water. Among those 445 pilgrims who completed the follow-up form, 21 (4.7%) developed one or more respiratory symptoms, of which sore throat and cough were the commonest (respectively 76.2% and 42.8%); 'possible ILI' and 'possible COVID-19' were present in 1.1% and 0.9% of pilgrims. Obesity was found to be a significant factor associated with the risk of developing RTIs (odds ratio = 4.45, 95% confidence interval 1.15-17.13). CONCLUSIONS: Hajj pilgrims are still at risk of respiratory infections. Further larger and controlled investigations are needed to assess the efficacy of hand hygiene during Hajj.

Discovery of Potential Antiviral Compounds against Hendra Virus by Targeting Its Receptor-Binding Protein (G) Using Computational Approaches.

Hendra virus (HeV) belongs to the paramyxoviridae family of viruses which is associated with the respiratory distress, neurological illness, and potential fatality of the affected individuals. So far, no competitive approved therapeutic substance is available for HeV. For that reason, the current research work was conducted to propose some novel compounds, by adopting a Computer Aided Drug Discovery approach, which could be used to combat HeV. The G attachment Glycoprotein (Ggp) of HeV was selected to achieve the primary objective of this study, as this protein makes the entry of HeV possible in the host cells. Briefly, a library of 6000 antiviral compounds was screened for potential drug-like properties, followed by the molecular docking of short-listed compounds with the Protein Data Bank (PDB) structure of Ggp. Docked complexes of top two hits, having maximum binding affinities with the active sites of Ggp, were further considered for molecular dynamic simulations of 200 ns to elucidate the results of molecular docking analysis. MD simulations and Molecular Mechanics Energies combined with the Generalized Born and Surface Area (MMGBSA) or Poisson-Boltzmann and Surface Area (MMPBSA) revealed that both docked complexes are stable in nature. Furthermore, the same methodology was used between lead compounds and HeV Ggp in complex with its functional receptor in human, Ephrin-B2. Surprisingly, no major differences were found in the results, which demonstrates that our identified compounds can also perform their action even when the Ggp is attached to the Ephrin-B2 ligand. Therefore, in light of all of these results, we strongly suggest that compounds (S)-5-(benzylcarbamoyl)-1-(2-(4-methyl-2-phenylpiperazin-1-yl)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide and 5-(cyclohexylcarbamoyl)-1-(2-((2-(3-fluorophenyl)-2-methylpropyl)amino)-2-oxoethyl)-6-oxo-3,6-dihydropyridin-1-ium-3-ide could be considered as potential therapeutic agents against HeV; however, further in vitro and in vivo experiments are required to validate this study.

Rescuing the Host Immune System by Targeting the Immune Evasion Complex ORF8-IRF3 in SARS-CoV-2 Infection with Natural Products Using Molecular Modeling Approaches.

The perennial emergence of SARS-CoV-2 and its new variants causing upper respiratory complexities since December 2019 has aggravated the pandemic situation around the world. SARS-CoV-2 encodes several proteins among which ORF8 is a novel factor that is unique to SARS-CoV-2 only and is reported to help the virus in disease severity and immune evasion. ORF8-IRF3 complex induces endoplasmic reticulum stress, thus helps in the evasion of immune response. Consequently, targeting the ORF8-IRF3 complex is considered as a prime target for the discovery of novel drugs against SARS-CoV-2. In this regard, computational methods are of great interest to fast track the identification and development of novel drugs. Virtual screening of South African Natural Compounds Database (SANCDB), followed by docking and molecular dynamics (MD) simulation analysis, were performed to determine novel natural compounds. Computational molecular search and rescoring of the SANCDB database followed by induced-fit docking (IFD) protocol identified Quercetin 3-O-(6″-galloyl)-beta-D-galactopyranoside (SANC00850), Tribuloside (SANC01050), and Rutin (SANC00867) are the best scoring compounds. Structural-dynamic properties assessment revealed that these three compounds have stable dynamics, compactness, and a higher number of hydrogen bonds. For validation, we used MM/GBSA, in silico bioactivity estimation and dissociation constant (KD) approaches, which revealed that these compounds are the more potent inhibitors of the ORF8-IRF3 complex and would rescue the host immune system potentially. These compounds need further in vitro and in vivo validations to be used as therapeutics against SARS-CoV-2 to rescue the host immune system during COVID-19 infection.

Annotation of Potential Vaccine Targets and Design of a Multi-Epitope Subunit Vaccine against Yersinia pestis through Reverse Vaccinology and Validation through an Agent-Based Modeling Approach.

Yersinia pestis is responsible for plague and major pandemics in Asia and Europe. This bacterium has shown resistance to an array of drugs commonly used for the treatment of plague. Therefore, effective therapeutics measurements, such as designing a vaccine that can effectively and safely prevent Y. pestis infection, are of high interest. To fast-track vaccine development against Yersinia pestis, herein, proteome-wide vaccine target annotation was performed, and structural vaccinology-assisted epitopes were predicted. Among the total 3909 proteins, only 5 (rstB, YPO2385, hmuR, flaA1a, and psaB) were shortlisted as essential vaccine targets. These targets were then subjected to multi-epitope vaccine design using different linkers. EAAK, AAY, and GPGPG as linkers were used to link CTL, HTL, and B-cell epitopes, and an adjuvant (beta defensin) was also added at the N-terminal of the MEVC. Physiochemical characterization, such as determination of the instability index, theoretical pI, half-life, aliphatic index, stability profiling, antigenicity, allergenicity, and hydropathy of the ensemble, showed that the vaccine is highly stable, antigenic, and non-allergenic and produces multiple interactions with immune receptors upon docking. In addition, molecular dynamics simulation confirmed the stable binding and good dynamic properties of the vaccine-TLR complex. Furthermore, in silico and immune simulation of the developed MEVC for Y. pestis showed that the vaccine triggered strong immune response after several doses at different intervals. Neutralization of the antigen was observed at the third day of injection. Conclusively, the vaccine designed here for Y. pestis produces an immune response; however, further immunological testing is needed to unveil its real efficacy.

Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity.

Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness.