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The entry of enveloped virus requires the fusion of viral and host cell membranes. An effective fusion inhibitor aiming at impeding such membrane fusion may emerge as a broad‐spectrum antiviral agent against a wide range of viral infections. Mycobacterium survives inside the phagosome by inhibiting phagosome–lysosome fusion with the help of a coat protein coronin 1. Structural analysis of coronin 1 and other WD40‐repeat protein suggest that the trp‐asp (WD) sequence is placed at distorted β‐meander motif (more exposed) in coronin 1. The unique structural feature of coronin 1 was explored to identify a simple lipo‐peptide sequence (myr‐WD), which effectively inhibits membrane fusion by modulating the interfacial order, water penetration, and surface potential. The mycobacterium inspired lipo‐dipeptide was successfully tested to combat type 1 influenza virus (H1N1) and murine coronavirus infections as a potential broad‐spectrum antiviral agent. [ABSTRACT FROM AUTHOR]

Acyl chain transfer, which perturbs the protonation equilibrium of amine and reduces the apparent pKa by 2.0–2.5 units, is used to develop a liposome-based drug delivery system. [ABSTRACT FROM AUTHOR]

Naturally secreted outer membrane vesicles (OMVs) from gut microbes carry diverse cargo, including proteins, nucleic acids, toxins, and many unidentified secretory factors. Bacterial OMVs can shuttle molecules across different cell types as a generalized secretion system, facilitating bacterial pathogenicity and self-survival. Numerous mucosal pathogens, including Campylobacter jejuni ( C. jejuni ), share a mechanism of harmonized secretion of major virulence factors. Intriguingly, as a common gut pathogen, C. jejuni lacks some classical virulence-associated secretion systems; alternatively, it often employs nanosized lipid-bound OMVs as an intensive strategy to deliver toxins, including secretory proteins, into the target cells. To better understand how the biophysical and compositional attributes of natural OMVs of C. jejuni regulate their cellular interactions to induce a biologically relevant host response, we conducted an in-depth morphological and compositional analysis of naturally secreted OMVs of C. jejuni . Next, we focused on understanding the mechanism of host cell-specific OMVs uptake from the extracellular milieu. We showed that intracellular perfusion of OMVs is mediated by cytosolic as well as multiple endocytic uptake processes due to the heterogenic nature, abundance of surface proteins, and membrane phospholipids acquired from the source bacteria. Furthermore, we used human and avian cells as two different host targets to provide evidence of target cell-specific preferential uptake of OMVs. Together, the present study provides insight into the unique functionality of natural OMVs of C. jejuni at the cellular interface, upholding their potential for multimodal use as prophylactic and therapeutic carriers.

The spike (S) protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) mediates a critical stage in infection, the fusion between viral and host membranes. The protein is categorized as a class I viral fusion protein and has two distinct cleavage sites that can be activated by proteases. The activation deploys the fusion peptide (FP) for insertion into the target cell membranes. Recent studies including our experiments showed that the FP was unable to modulate the kinetics of fusion at a low peptide-to-lipid ratio akin to the spike density at the viral surface. Therefore, we modified the C terminus of FP and attached a myristoyl chain (C-myr-FP) to restrict the C terminus near to the interface, bridge both membranes, and increase the effective local concentration. The lipidated FP (C-myr-FP) of SARS-CoV-2 greatly accelerates membrane fusion at a low peptide-to-lipid ratio as compared to the FP with no lipidation. Biophysical experiments suggest that C-myr-FP adopts a helical structure, perturbs the membrane interface, and increases water penetration to catalyze fusion. Scrambled peptide (C-myr-sFP) and truncated peptide (C-myr-8FP) could not significantly catalyze the fusion, thus suggesting the important role of myristoylation and the N terminus. C-myr-FP enhances murine coronavirus infection by promoting syncytia formation in L2 cells. The C-terminal lipidation of the FP might be a useful strategy to induce artificial fusion in biomedical applications., (© 2022 Wiley-VCH GmbH.)

Acyl chain transfer, which perturbs the protonation equilibrium of amine and reduces the apparent pKa by 2.0-2.5 units, is used to develop a liposome-based drug delivery system.