Vaccines are effective interventions that can reduce the high burden of diseases globally. However, public vaccine hesitancy is a pressing problem for public health authorities. With the availability of COVID-19 vaccines, little information is available on the public acceptability and attitudes towards the COVID-19 vaccines in Jordan. This study aimed to investigate the acceptability of COVID-19 vaccines and its predictors in addition to the attitudes towards these vaccines among public in Jordan. An online, cross-sectional, and self-administered questionnaire was instrumentalized to survey adult participants from Jordan on the acceptability of COVID-19 vaccines. Logistic regression analysis was used to find the predictors of COVID-19 vaccines’ acceptability. A total of 3,100 participants completed the survey. The public acceptability of COVID-19 vaccines was fairly low (37.4%) in Jordan. Males (OR = 2.488, 95CI% = 1.834–3.375, p < .001) and those who took the seasonal influenza vaccine (OR = 2.036, 95CI% = 1.306–3.174, p = .002) were more likely to accept COVID-19 vaccines. Similarly, participants who believed that vaccines are generally safe (OR = 9.258, 95CI% = 6.020–14.237, p < .001) and those who were willing to pay for vaccines (OR = 19.223, 95CI% = 13.665–27.042, p < .001), once available, were more likely to accept the COVID-19 vaccines. However, those above 35 years old (OR = 0.376, 95CI% = 0.233–0.607, p < .001) and employed participants (OR = 0.542, 95CI% = 0.405–0.725, p < .001) were less likely to accept the COVID-19 vaccines. Moreover, participants who believed that there was a conspiracy behind COVID-19 (OR = 0.502, 95CI% = 0.356–0.709, p < .001) and those who do not trust any source of information on COVID-19 vaccines (OR = 0.271, 95CI% = 0.183–0.400, p < .001), were less likely to have acceptance towards them. The most trusted sources of information on COVID-19 vaccines were healthcare providers. Systematic interventions are required by public health authorities to reduce the levels of vaccines’ hesitancy and improve their acceptance. We believe these results and specifically the low rate of acceptability is alarming to Jordanian health authorities and should stir further studies on the root causes and the need of awareness campaigns. These interventions should take the form of reviving the trust in national health authorities and structured awareness campaigns that offer transparent information about the safety and efficacy of the vaccines and the technology that was utilized in their production.

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A major problem in the discovery of new biologically active compounds from natural products is the re-isolation of known compounds. Such re-isolations waste time and resources, distracting chemists from more promising leads. To address this problem, dereplication strategies are needed that enable crude extracts to be screened for the presence of known compounds before isolation efforts are initiated. In a project to identify anticancer drug leads from filamentous fungi, a significant dereplication challenge arises, as the taxonomy of the source materials are rarely known, and, thus, the literature cannot be probed to identify likely known compounds. An ultra-performance liquid chromatography-photodiode array-high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS) method was developed for dereplication of fungal secondary metabolites in crude culture extracts. A database was constructed by recording HRMS and MS/MS spectra of fungal metabolites, utilizing both positive- and negative-ionization modes. Additional details, such as UV-absorption maxima and retention times, were also recorded. Small-scale cultures that showed cytotoxic activities were dereplicated before engaging in the scale-up or purification processes. Using these methods, approximately 50% of the cytotoxic extracts could be eliminated from further study after the confident identification of known compounds. The specific attributes of this dereplication methodology include a focus on bioactive secondary metabolites from fungi, the use of a 10-min chromatographic method, and the inclusion of both HRMS and MS/MS data.

The endophytic fungus Penicillium restrictum was isolated from the stems of a milk thistle (Silybum marianum) plant. In culture, the fungus produced distinct red guttates, which have been virtually uninvestigated, particularly from the standpoint of chemistry. Hence, this study examined the chemical mycology of P. restrictum and, in doing so, uncovered a series of both known and new polyhydroxyanthraquinones (1–9). These compounds were quorum sensing inhibitors in a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA), with IC50 values ranging from 8 to 120 μM, suggesting antivirulence potential for the compounds. Moreover, the spatial and temporal distribution of the polyhydroxyanthraquinones was examined in situ via desorption electrospray ionization–mass spectrometry (DESI-MS) imaging, demonstrating the first application of this technique to a guttate-forming fungus and revealing both the concentration of secondary metabolites at the ventral surface of the fungus and their variance in colonies of differing ages.

d Antibiotic-resistant pathogens are a global health threat. Small molecules that inhibit bacterial virulence have been suggested as alternatives or adjuncts to conventional antibiotics, as they may limit pathogenesis and increase bacterial susceptibility to host killing. Staphylococcus aureus is a major cause of invasive skin and soft tissue infections (SSTIs) in both the hospital and community settings, and it is also becoming increasingly antibiotic resistant. Quorum sensing (QS) mediated by the accessory gene regulator (agr) controls virulence factor production essential for causing SSTIs. We recently identified -hydroxyemodin (OHM), a polyhydroxyanthraquinone isolated from solid-phase cultures of Penicillium restrictum, as a suppressor of QS and a compound sought for the further characterization of the mechanism of action. At concentrations that are nontoxic to eukaryotic cells and subinhibitory to bacterial growth, OHM prevented agr signaling by all four S. aureus agr alleles. OHM inhibited QS by direct binding to AgrA, the response regulator encoded by the agr operon, preventing the interaction of AgrA with the agr P2 promoter. Importantly, OHM was efficacious in a mouse model of S. aureus SSTI. Decreased dermonecrosis with OHM treatment was associated with enhanced bacterial clearance and reductions in inflammatory cytokine transcription and expression at the site of infection. Furthermore, OHM treatment enhanced the immune cell killing of S. aureus in vitro in an agr-dependent manner. These data suggest that bacterial disarmament through the suppression of S. aureus QS may bolster the host innate immune response and limit inflammation.

Variation in the growing environment can have significant impacts on the quantity and diversity of fungal secondary metabolites. In the industrial setting, optimization of growing conditions can lead to significantly increased production of a compound of interest. Such optimization becomes challenging in a drug-discovery screening situation, as the ideal conditions for one organism may induce poor metabolic diversity for a different organism. Here, the impact of different media types, including six liquid media and five solid media, on the secondary metabolite production of three fungal strains was examined in the context of the drug-discovery screening process. The relative production of marker compounds was used to evaluate the usefulness and reliability of each medium for the purpose of producing secondary metabolites.

Fourteen new resorcylic acid lactones (1–14) were isolated from an organic extract of a culture of a freshwater aquatic fungus Halenospora sp. originating from a stream in North Carolina. The structures were elucidated using a set of spectroscopic and spectrometric techniques. The absolute configuration of one representative member of the compounds (7) was assigned using X-ray crystallography of an analogue that incorporated a heavy atom, whereas for compounds 8–11, a modified Mosher’s ester method was utilized. The relative configurations of compounds 12–14 were determined on the basis of NOE data. Compounds 12–14 were proposed as artifacts produced by intramolecular cycloetherification of the ε-hydroxy-α,β-unsaturated ketone moieties of the parent compounds during the purification processes. The isolated compounds, except for 8 and 12, were tested against the MDA-MB-435 (melanoma) and HT-29 (colon) cancer cell lines. Compound 5 was the most potent, with IC50 values of 2.9 and 7.5 μM, respectively. The compounds were evaluated as TAK1–TAB1 inhibitors but were found to be inactive.

Ambient ionization mass spectrometry techniques have recently become prevalent in natural product research due to their ability to examine secondary metabolites in situ. These techniques retain invaluable spatial and temporal details that are lost through traditional extraction processes. However, most ambient ionization techniques do not collect mutually supportive data, such as chromatographic retention times and/or UV/vis spectra, and this can limit the ability to identify certain metabolites, such as differentiating isomers. To overcome this, the droplet–liquid microjunction–surface sampling probe (droplet–LMJ–SSP) was coupled with UPLC–PDA–HRMS–MS/MS, thus providing separation, retention times, MS data, and UV/vis data used in traditional dereplication protocols. By capturing these mutually supportive data, the identity of secondary metabolites can be confidently and rapidly assigned in situ. Using the droplet–LMJ–SSP, a protocol was constructed to analyze the secondary metabolite profile of fungal cultures without any sample preparation. The results demonstrate that fungal cultures can be dereplicated from the Petri dish, thus identifying secondary metabolites, including isomers, and confirming them against reference standards. Furthermore, heat maps, similar to mass spectrometry imaging, can be used to ascertain the location and relative concentration of secondary metabolites directly on the surface and/or surroundings of a fungal culture.