It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.

Background: Early initiation of treatment is essential for treatment of avian influenza A/H5N1 viral infection in humans, as the disease can lead to rapid development of severe pneumonia which can result in death. Contact with infected poultry is known to be a significant risk factor for contraction of H5N1 infection. However, handling and encountering poultry are a part of most peoples' daily lives, especially in rural communities in Vietnam where epidemic outbreaks among poultry have been continuously reported. Enhancing proper knowledge relating to H5N1 and to the importance of early initiation of treatment are crucial. The aim of this study was to develop an effective educational program to enhance awareness of H5N1 and motivate people to access to health care earlier when H5N1 infection is suspected or likely. Methodology and Principal Findings: A study was conducted in two agricultural communities (intervention and control groups) in the Ninh Binh province in Vietnam, where epidemic outbreaks of avian influenza have recently occurred in birds. A unique educational intervention was developed and provided to the intervention group, and no intervention was provided to the control group. A knowledge, attitude and practice (KAP) survey was conducted in both groups with a faceto- face interview by trained local healthcare workers at time points before and after the educational intervention. KAP scores were compared between the different time points and between the groups. How educational intervention influenced awareness relating to H5N1 and accessibility of healthcare in the population was analyzed. The study indicated an increased awareness of H5N1 and increased reliance on local health care workers. Conclusions: The novel educational program which was developed for this study impacted awareness of H5N1, and resulted in more people seeking early access to healthcare, and also resulted in earlier medical intervention for patients with H5N1 avian influenza infection in Vietnam. [ABSTRACT FROM AUTHOR]