Repurposing fusion inhibitor peptide against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex. Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.

Antiviral Peptides as Promising Therapeutics against SARS-CoV-2.

Over 50 peptides, which were known to inhibit SARS-CoV-1, were computationally screened against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. Based on the binding affinity and interaction, 15 peptides were selected, which showed higher affinity compared to the α-helix of the human ACE2 receptor. Molecular dynamics simulation demonstrated that two peptides, S2P25 and S2P26, were the most promising candidates, which could potentially block the entry of SARS-CoV-2. Tyr489 and Tyr505 residues present in the "finger-like" projections of the RBD were found to be critical for peptide interaction. Hydrogen bonding and hydrophobic interactions played important roles in prompting peptide-protein binding and interaction. Structure-activity relationship indicated that peptides containing aromatic (Tyr and Phe), nonpolar (Pro, Gly, Leu, and Ala), and polar (Asn, Gln, and Cys) residues were the most significant contributors. These findings can facilitate the rational design of selective peptide inhibitors targeting the spike protein of SARS-CoV-2.

Development of the community midwifery education initiative and its influence on women's health and empowerment in Afghanistan: a case study.

BACKGROUND: Political transition in Afghanistan enabled reconstruction of the destroyed health system. Maternal health was prioritised due to political will and historically high mortality. However, severe shortages of skilled birth attendants--particularly in rural areas--hampered safe motherhood initiatives. The Community Midwifery Education (CME) programme began training rural midwives in 2002, scaling-up nationally in 2005. METHODS: This case study analyses CME development and implementation to help determine successes and challenges. Data were collected through documentary review and key informant interviews. Content analysis was informed by Walt and Gilson's policy triangle framework. RESULTS: The CME programme has contributed to consistently positive indicators, including up to a 1273/100,000 reduction in maternal mortality ratios, up to a 28% increase in skilled deliveries, and a six-fold increase in qualified midwives since 2002. Begun as a small pilot, CME has gained support of international donors, the Afghan government, and civil society. CONCLUSION: CME is considered by stakeholders to be a positive model for promoting women's education, employment, and health. However, its future is threatened by insecurity, corruption, lack of regulation, and funding uncertainties. Strategic planning and resource mobilisation are required for it to achieve its potential of transforming maternal healthcare in Afghanistan.

Perspectives on reproductive healthcare delivered through a basic package of health services in Afghanistan: a qualitative study.

BACKGROUND: Contracting-out non-state providers to deliver a minimum package of essential health services is an increasingly common health service delivery mechanism in conflict-affected settings, where government capacity and resources are particularly constrained. Afghanistan, the longest-running example of Basic Package of Health Services (BPHS) contracting in a conflict-affected setting, enables study of how implementation of a national intervention influences access to prioritised health services. This study explores stakeholder perspectives of sexual and reproductive health (SRH) services delivered through the BPHS in Afghanistan, using Bamyan Province as a case study. METHODS: Twenty-six in-depth interviews were conducted with health-system practitioners (e.g. policy/regulatory, middle management, frontline providers) and four focus groups with service-users. Inductive thematic coding used the WHO Health System Framework categories (i.e. service delivery, workforce, medicines, information, financing, stewardship), while allowing for emergent themes. RESULTS: Improvements were noted by respondents in all health-system components discussed, with significant improvements identified in service coverage and workforce, particularly improved gender balance, numbers, training, and standardisation. Despite improvements, remaining weaknesses included service access and usage - especially in remote areas, staff retention, workload, and community accountability. CONCLUSIONS: By including perspectives on SRH service provision and BPHS contracting across health-system components and levels, this study contributes to broader debates on the effects of contracting on perceptions and experiences among practitioners and service-users in conflict-affected countries.

Malaria control under the Taliban regime: insecticide-treated net purchasing, coverage, and usage among men and women in eastern Afghanistan.

BACKGROUND: Scaling up insecticide-treated mosquito net (ITN) coverage is a key malaria control strategy even in conflict-affected countries 12. Socio-economic factors influence access to ITNs whether subsidized or provided free to users. This study examines reported ITN purchasing, coverage, and usage in eastern Afghanistan and explores women's access to health information during the Taliban regime (1996-2001). This strengthens the knowledge base on household-level health choices in complex-emergency settings. METHODS: Fifteen focus group discussions (FGDs) and thirty in-depth interviews were conducted with men and women from ITN-owning and non-owning households. FGDs included rank ordering, pile sorting and focused discussion of malaria knowledge and ITN purchasing. Interviews explored general health issues, prevention and treatment practices, and women's malaria knowledge and concerns. Seven key informant interviews with health-related workers and a concurrent survey of 200 ITN-owning and 214 non-owning households were used to clarify or quantify findings. RESULTS: Malaria knowledge was similar among men and women and ITN owners and non-owners. Women reported obtaining health information through a variety of sources including clinic staff, their husbands who had easier access to information, and particularly female peers. Most participants considered ITNs very desirable, though not usually household necessities. ITN owners reported more household assets than non-owners. Male ITN owners and non-owners ranked rugs and ITNs as most desired, while women ranked personal assets such as jewellery highest. While men were primarily responsible for household decision-making and purchasing, older women exerted considerable influence. Widow-led and landless households reported most difficulties purchasing ITNs. Most participants wanted to buy ITNs only if they could cover all household members. When not possible, preferential usage was given to women and children. CONCLUSIONS: Despite restricted access to health facilities and formal education, Afghan women were surprisingly knowledgeable about the causes of malaria and the value of ITNs in prevention. Inequities in ITN usage were noted between rather than within households, with some unable to afford even one ITN and others not wanting ITNs unless all household members could be protected. Malaria knowledge thus appears a lesser barrier to ITN purchasing and coverage in eastern Afghanistan than are pricing and distribution strategies.

Antibacterial activity of synthesized 2,4,5-trisubstituted imidazole derivatives.

Some novel chemically synthesized 2,4,5-trisubstituted imidazoles from aryl aldehydes and 1,2-diketones or alpha-hydroxyketone were screened against eight different human pathogenic bacteria and fungi. Seven compounds were found to be active against different bacteria. These compounds showed variation in activity and were found to be active against Gram-positive as well as Gram-negative bacteria. Compound 4-(4,5-diphenyl-1H-imidazol-2-yl)-phenol, 3d was the only compound which showed activity against Klebsiella pneumoniae while rest of the compounds did not show significant activity against this micro-organism. Minimum inhibitory concentrations of the compounds were in the range of 0.50 to 6.1 microg/mL and minimum bactericidal concentration ranges from 1.11 to 12.9 microg/mL. The candidature of active compounds to be an effective and novel drug was examined based on Lipinski's rule of Five which explained ClogP, LogS, H-bond acceptors, H-Bond donors and rotational bonds. Compounds 3a-d and 3f satisfies Lipinski's rule of Five and could be proposed as potent new antibacterial drugs.