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Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at finding antivirals capable of interfering with the fusion mechanism, mainly by designing peptides on the two heptad-repeat regions present in class I viral fusion proteins. Here, we aimed to evaluate the anti-SARS-CoV-2 activity of the FP sequence conjugated to a tetravalent dendrimer through a classical organic nucleophilic substitution reaction (SN2) using a synthetic bromoacetylated peptide mimicking the FP and a branched scaffold of poly-L-Lysine functionalized with cysteine residues. We found that the FP peptide conjugated to the dendrimer, unlike the monomeric FP sequence, has virucidal activity by impairing the attachment of SARS-CoV-2 to cells. Furthermore, we found that the peptide dendrimer does not have the same effects on other coronaviruses, demonstrating that it is selective against SARS-CoV-2.

Emerging viruses pose an important global public health challenge, and early action is needed to control their spread. The Bunyaviridae family contains a great number of arboviruses which are potentially pathogenic for humans. For example, phleboviruses affect a large range of hosts, including humans and animals. Some infections usually have an asymptomatic course, but others lead to severe complications, such as Toscana virus, which is able to cause meningitis and encephalitis. Unfortunately, to date, no vaccines or antiviral treatments have been found. In the present study, we evaluated the effect of melittin-related peptides, namely the frog-derived RV-23 and AR-23, on sandfly fever Naples virus infection in vitro. Both peptides exhibited a strong antiviral activity by targeting the viral particles and blocking the virus–cell interaction. Their action was directed to an early phase of SFNV infection, in particular at viral adsorption on host cells, by interfering with the binding of common glycosaminoglycan receptors. Given the better antimicrobial behavior of AR-23 and RV-23 compared to melittin in terms of selectivity, our studies expand our understanding of the potential of these peptides as antimicrobials and stimulate further investigations in the direction of novel antiviral strategies against phlebovirus infection.

Staphylococci, including Staphylococcus aureus and Staphylococcus epidermidis, are important human pathogens associated with potentially life-threatening infections. Their great biofilm-producing ability and the development of resistance mechanisms often account for therapeutic failure. Hence, the scientific community has devoted intensive efforts to the development of antimicrobial compounds active against both planktonic and sessile bacterial populations. Contextually, antimicrobial peptides (AMPs) are natural peptides produced by the innate immunity of every organism, representing a potential new therapeutic solution against human microbial pathogens. Our work focused on the in vitro activity of Oreoch-1, an AMP from the gills of Nile tilapia (Oreochromis niloticus), against standard and clinical S. aureus and S. epidermidis strains. Firstly, the cytotoxicity profile of Oreoch-1 was determined in human colon carcinoma cells. Secondly, its antibacterial spectrum was explored against staphylococcal strains to set up the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Our results highlighted an antibacterial activity in the range 6.25–25 μM, with a general bacteriostatic effect. Therefore, the biofilm-inhibitory property was assessed against S. aureus ATCC 25923 and S. epidermidis ATCC 35984, indicating a significant reduction in S. aureus biomass at sub-MIC concentrations. Overall, our study indicates Oreoch-1 as a promising new therapeutic weapon against staphylococcal infections.

Given the emergence of the coronavirus disease 2019 (COVID-19), zoonoses have raised in the spotlight of the scientific community. Animals have a pivotal role not only for this infection, but also for many other recent emerging and re-emerging viral diseases, where they may represent both intermediate hosts and/or vectors for zoonoses diffusion. Today, roughly two-thirds of human infections are derived from animal origins; therefore, the search for new broad-spectrum antiviral molecules is mandatory to prevent, control and eradicate future epidemic outbreaks. Host defense peptides, derived from skin secretions of amphibians, appear as the right alternative to common antimicrobial drugs. They are cationic peptides with an amphipathic nature widely described as antibacterial agents, but less is reported about their antiviral potential. In the present study, we evaluated the activity of five amphibian peptides, namely RV-23, AR-23, Hylin-a1, Deserticolin-1 and Hylaseptin-P1, against a wide panel of enveloped animal viruses. A strong virucidal effect was observed for RV-23, AR-23 and Hylin-a1 against bovine and caprine herpesviruses, canine distemper virus, bovine viral diarrhea virus, and Schmallenberg virus. Our results identified these three peptides as potential antiviral-led candidates with a putative therapeutic effect against several animal viruses.

The COVID-19 pandemic has made it clear that there is a crucial need for the design and development of antiviral agents that can efficiently reduce the fatality rate caused by infectious diseases. The fact that coronavirus mainly enters through the nasal epithelial cells and spreads through the nasal passage makes the nasal delivery of antiviral agents a promising strategy not only to reduce viral infection but also its transmission. Peptides are emerging as powerful candidates for antiviral treatments, showing not only a strong antiviral activity, but also improved safety, efficacy, and higher specificity against viral pathogens. Based on our previous experience on the use of chitosan-based nanoparticles to deliver peptides intra-nasally the current study aimed to explore the delivery of two-novel antiviral peptides making use of nanoparticles consisting of HA/CS and DS/CS. The antiviral peptides were chemically synthesized, and the optimal conditions for encapsulating them were selected through a combination of physical entrapment and chemical conjugation using HA/CS and DS/CS nanocomplexes. Finally, we evaluated the in vitro neutralization capacity against SARS-CoV-2 and HCoV-OC43 for potential use as prophylaxis or therapy.

In recent years, the resistance of pathogenic microorganisms to common antimicrobial agents has raised to a severe public health problem. The moderate and wise use of antimicrobials and the prevention of infections are the most effective strategies for decreasing the spread and development of resistance. Therefore, the World Health Organization (WHO) has intensified the search for new drugs to fight emerging pathogens. Antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), play a crucial role in innate immunity, representing one of the first line of defense against microbial attacks. In this study, we evaluated the antibacterial activity of the AMP named Hylin-a1 (derived from the skin of the frog Heleioporus albopunctatus) against Staphylococcus aureus strains. S. aureus represents a commensal bacterium but also the principal causative agent of several human infections, including bacteremia, endocarditis, skin and device-related infections. Hylin-a1 toxicity was evaluated on human keratinocytes; once the non-cytotoxic concentration range was determined, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were analyzed, and time-killing assays were performed to verify the bacteriostatic and/or bactericidal activity of the peptide. We found that Hylin-a1 exerted a bacteriostatic action against most of the tested strains, with 90% inhibition at the concentration of 6.25 μM. Noteworthy, the peptide at a very low concentration (~3 μM) significantly blocked the growth of β-lactam- and methicillin-resistant S. aureus. The levels of interleukin (IL)-1β, IL-6 and IL-8 were quantified through a molecular assay, indicating that the peptide was able also to regulate the inflammatory response following bacterial infection. The effect of Hylin-a1 on S. aureus cell morphology was also evaluated. Altogether, these results indicate the high therapeutic potential of Hylin-a1 against a wide variety of clinical manifestations caused by S. aureus.

The continuous and rapid spread of the COVID-19 pandemic has emphasized the need to seek new therapeutic and prophylactic treatments. Peptide inhibitors are a valid alternative approach for the treatment of emerging viral infections, mainly due to their low toxicity and high efficiency. Recently, two small nucleotide signatures were identified in the genome of some members of the Coronaviridae family and many other human pathogens. In this study, we investigated whether the corresponding amino acid sequences of such nucleotide sequences could have effects on the viral infection of two representative human coronaviruses: HCoV-OC43 and SARS-CoV-2. Our results showed that the synthetic peptides analyzed inhibit the infection of both coronaviruses in a dose-dependent manner by binding the RBD of the Spike protein, as suggested by molecular docking and validated by biochemical studies. The peptides tested do not provide toxicity on cultured cells or human erythrocytes and are resistant to human serum proteases, indicating that they may be very promising antiviral peptides.

Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells.