To Örebro University

Flaviviruses, including West Nile virus, Zika virus, and Dengue virus, pose global health challenges due to their distribution, pathogenicity, and lack of effective treatments or vaccines. This study investigated the antiviral activity of novel truncated peptides derived from the two-peptide plantaricins PLNC8 αβ, PlnEF, PlnJK, and PlnA. The antiviral potential was predicted using machine learning tools, followed by in vitro evaluation against the Kunjin virus using plaque reduction assays in Vero cells. Molecular docking assessed peptide interactions with KUNV and ZIKV. Full-length and truncated peptides from PlnA, PlnE, PlnF, PlnJ, and PlnK demonstrated limited antiviral efficacy against KUNV in vitro, despite in silico predictions suggesting antiviral potential for PlnA, PlnE, and PlnJ. Large discrepancies were observed between the predicted and experimentally determined activities. However, complementary two-peptide plantaricins PlnEF and PlnJK exhibited significant synergistic effects. Furthermore, the truncated peptides PLNC8 α1-15 and PLNC8 β1-20 reduced KUNV viral load by over 90%, outperforming their full-length counterparts. Molecular docking revealed interactions of PLNC8 α and PLNC8 β, and their truncated variants, with KUNV and ZIKV, suggesting a mechanism involving viral envelope disruption. These findings highlight the potential of plantaricin-derived peptides as promising antiviral candidates against flaviviruses, warranting further investigation into their mechanisms and applications.

PLNC8 alpha beta is a cationic antimicrobial peptide that previously has been reported to express both antibacterial and antiviral properties. This study aimed to further elucidate the antiviral effects of PLNC8 alpha beta and its impact on virus-induced cytotoxicity and inflammatory signaling in human alveolar epithelial cells (A549) infected with the flavivirus Kunjin. Complementary in silico analyses using molecular dynamics (MD) simulation were conducted to investigate the mechanism of action of PLNC8 alpha beta by studying the interaction of PLNC8 alpha and beta with models of a flavivirus membrane and a eukaryotic plasma membrane, respectively. Our findings demonstrated that PLNC8 alpha beta significantly reduces both extracellular and intracellular viral loads, as confirmed by plaque reduction assays and RT-PCR. The peptide also mitigated virus-induced cytotoxicity and inflammation. Notably, PLNC8 alpha beta modulated the virus-induced dysregulation of key signaling and inflammatory genes, such as TLR9, TLR3, NOD2, FOS, JUN, IL6, and CXCL8. MD simulation revealed that PLNC8 alpha beta exhibits higher binding affinity for a flavivirus membrane model compared to a model of the plasma membrane, likely due to stronger electrostatic interactions with anionic phospholipids. This selective interaction possibly accounts for a potent antiviral activity of PLNC8 alpha beta combined with a minimal cytotoxicity toward human cells. Overall, PLNC8 alpha beta shows significant promise as an antiviral agent against flavivirus infections and warrants further exploration for peptide-based antiviral therapies.

Background: Vaccines are an essential part of public health interventions to mitigate the devastating health and non-health impacts of COVID-19 pandemic. Despite the fact that Sudan launched the COVID-19 vaccination program in March 2021, only 10% of the population received their two primary doses of vaccines by the end of May 2022. This delayed uptake of vaccines obviously warrants investigation. Therefore, we have conducted this study to evaluate the knowledge, attitude and acceptance of the general population in Sudan toward COVID-19 vaccines.

Methodology: A descriptive cross-sectional community-based study. The data were collected using an electronic questionnaire from 403 individuals living in Khartoum, Sudan. The data were processed using the Statistical Package for Social Sciences (SPSS), and data analysis was performed using appropriate tests.

Results: 51% of the participants were found to have sufficient knowledge about the COVID-19 vaccine, and the knowledge level is higher among those educated beyond the secondary school and those who were employed. Among those unvaccinated, only 47% of the participants expressed their intention to take the vaccine when offered to them. The major reason for not trusting the vaccine is safety concerns expressed by 65.5% of the unvaccinated.

Conclusion: Higher education levels and employment were associated with an increase in sufficient knowledge about the vaccine in around half of the participants. However, most of participants had not taken the vaccine at the time of the study, and the trust in vaccines is not high. Effective interventions by the health authorities are needed to address these issues in order to accelerate the COVID-19 vaccination program in Sudan.

Background: Coronavirus disease 2019 (COVID-19) has caused a global public health crisis. The disease is known to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, but the detailed characteristics of the immune response to this novel virus have not been fully elucidated yet. In this study, we aimed to determine the level of immunoglobulin G (IgG) antibodies and their correlation with clinical features at three time points postinfection in a group of patients in Saudi Arabia.

Method: In this prospective observational study, we collected the demographic and clinical data from 43 polymerase chain reaction (PCR)-confirmed patients and measured the COVID-19 antispike IgG levels at three different visits.

Result: The seroconversion rate after COVID-19 infection was 88.4% in the study participants, with no significant changes in the IgG levels through the three visits. The duration of shortness of breath had a significant positive correlation with the IgG level of the patients. Using the logistic regression model, participants having coughs were found to be 12.48 times more likely to develop positive IgG. The IgG levels were less in smokers than nonsmokers [Odds ratio = 6.42 (95% CI 2.11-19.48); P = 0.001].

Conclusion: Positive IgG levels have been developed in most COVID-19 patients and did not significantly change over 3 months following the diagnosis. The level of IgG antibodies was found to be significantly associated with the presence of cough, duration of shortness of breath, and the smoking habit of the patients. These findings have clinical and public health significance and need to be validated in larger studies in different populations.

Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 αβ, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 αβ is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 αβ against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus-1 (HIV-1). The concentration of PLNC8 αβ that is required to eliminate all the infective virus particles is in the range of nanomolar (nM) to micromolar (μM), which is surprisingly efficient considering the high content of cholesterol (8–35%) in their lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)/Golgi complex, e.g. SARS-CoV-2 and flaviviruses, are considerably more susceptible to PLNC8 αβ, compared to viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. Development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limit virus dissemination and spreading between individuals. PLNC8 αβ can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, more or less independent of virus antigenic mutations, which faces many antiviral drugs and vaccines.