The GC% landscape of the Nucleocytoviricota.

Genomic studies on sequence composition employ various approaches, such as calculating the proportion of guanine and cytosine within a given sequence (GC% content), which can shed light on various aspects of the organism's biology. In this context, GC% can provide insights into virus-host relationships and evolution. Here, we present a comprehensive gene-by-gene analysis of 61 representatives belonging to the phylum Nucleocytoviricota, which comprises viruses with the largest genomes known in the virosphere. Parameters were evaluated not only based on the average GC% of a given viral species compared to the entire phylum but also considering gene position and phylogenetic history. Our results reveal that while some families exhibit similar GC% among their representatives (e.g., Marseilleviridae), others such as Poxviridae, Phycodnaviridae, and Mimiviridae have members with discrepant GC% values, likely reflecting adaptation to specific biological cycles and hosts. Interestingly, certain genes located at terminal regions or within specific genomic clusters show GC% values distinct from the average, suggesting recent acquisition or unique evolutionary pressures. Horizontal gene transfer and the presence of potential paralogs were also assessed in genes with the most discrepant GC% values, indicating multiple evolutionary histories. Taken together, to the best of our knowledge, this study represents the first global and gene-by-gene analysis of GC% distribution and profiles within genomes of Nucleocytoviricota members, highlighting their diversity and identifying potential new targets for future studies.

Isolation and In Vitro Biological Evaluation of Triterpenes from Salacia grandifolia Leaves.

Salacia grandifolia is naturally found in the Atlantic Forest regions of Brazil. Despite the pharmacological potential of plants from the Salacia genus, phytochemical studies on this species have not been reported in literature. A new triterpene, 28-hydroxyfriedelane-3,15-dione (1), and seven known compounds (friedelan-3-one (2), friedelan-3ß-ol (3), friedelane-3,15-dione (4), 15α-hydroxyfriedelan-3-one (5), 28-hydroxyfriedelan-3-one (6), 30-hydroxyfriedelan-3-one (7), and 29-hydroxyfriedelan-3-one (8)) were obtained from the hexane extract of Salacia grandifolia leaves. These isolated compounds and three extracts, hexane (EH), chloroform (EC), and ethyl acetate (EAE), were assessed for their potential biological activities, which consisted in the evaluation of antiviral activity against a murine coronavirus, mouse hepatitis virus 3 (MHV-3), antibacterial activity against the susceptible and methicillin-resistant Staphylococcus aureus (MRSA), and antileukemia activity against the THP-1 and K-562 cell lines. The extracts EH and EAE along with the triterpenes 1 and 6 exhibited moderate to high antiviral activity, with emphasis on 6, which presented an EC50 value of 2.9 ± 0.3 µM. None of the compounds presented antibacterial activity against the tested strains. The evaluated compounds 1, 4, 6 and 7 exhibited low cytotoxic activity against the tested leukemia cell lines. Taken together, this study comprises an overview for the potential of the Salacia grandifolia biological activities, including a new isolated triterpene.

A long-term prospecting study on giant viruses in terrestrial and marine Brazilian biomes.

The discovery of mimivirus in 2003 prompted the search for novel giant viruses worldwide. Despite increasing interest, the diversity and distribution of giant viruses is barely known. Here, we present data from a 2012-2022 study aimed at prospecting for amoebal viruses in water, soil, mud, and sewage samples across Brazilian biomes, using Acanthamoeba castellanii for isolation. A total of 881 aliquots from 187 samples covering terrestrial and marine Brazilian biomes were processed. Electron microscopy and PCR were used to identify the obtained isolates. Sixty-seven amoebal viruses were isolated, including mimiviruses, marseilleviruses, pandoraviruses, cedratviruses, and yaraviruses. Viruses were isolated from all tested sample types and almost all biomes. In comparison to other similar studies, our work isolated a substantial number of Marseillevirus and cedratvirus representatives. Taken together, our results used a combination of isolation techniques with microscopy, PCR, and sequencing and put highlight on richness of giant virus present in different terrestrial and marine Brazilian biomes.

Design, development, and validation of multi-epitope proteins for serological diagnosis of Zika virus infections and discrimination from dengue virus seropositivity.

Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is the causative agent of Zika fever, a mild and frequent oligosymptomatic disease in humans. Nonetheless, on rare occasions, ZIKV infection can be associated with Guillain-Barré Syndrome (GBS), and severe congenital complications, such as microcephaly. The oligosymptomatic disease, however, presents symptoms that are quite similar to those observed in infections caused by other frequent co-circulating arboviruses, including dengue virus (DENV). Moreover, the antigenic similarity between ZIKV and DENV, and even with other members of the Flaviviridae family, complicates serological testing due to the high cross-reactivity of antibodies. Here, we designed, produced in a prokaryotic expression system, and purified three multiepitope proteins (ZIKV-1, ZIKV-2, and ZIKV-3) for differential diagnosis of Zika. The proteins were evaluated as antigens in ELISA tests for the detection of anti-ZIKV IgG using ZIKV- and DENV-positive human sera. The recombinant proteins were able to bind and detect anti-ZIKV antibodies without cross-reactivity with DENV-positive sera and showed no reactivity with Chikungunya virus (CHIKV)- positive sera. ZIKV-1, ZIKV-2, and ZIKV-3 proteins presented 81.6%, 95%, and 66% sensitivity and 97%, 96%, and 84% specificity, respectively. Our results demonstrate the potential of the designed and expressed antigens in the development of specific diagnostic tests for the detection of IgG antibodies against ZIKV, especially in regions with the circulation of multiple arboviruses.

Machine Learning-Based Virtual Screening of Antibacterial Agents against Methicillin-Susceptible and Resistant Staphylococcus aureus.

The application of computer-aided drug discovery (CADD) approaches has enabled the discovery of new antimicrobial therapeutic agents in the past. The high prevalence of methicillin-resistantStaphylococcus aureus(MRSA) strains promoted this pathogen to a high-priority pathogen for drug development. In this sense, modern CADD techniques can be valuable tools for the search for new antimicrobial agents. We employed a combination of a series of machine learning (ML) techniques to select and evaluate potential compounds with antibacterial activity against methicillin-susceptible S. aureus (MSSA) and MRSA strains. In the present study, we describe the antibacterial activity of six compounds against MSSA and MRSA reference (American Type Culture Collection (ATCC)) strains as well as two clinical strains of MRSA. These compounds showed minimal inhibitory concentrations (MIC) in the range from 12.5 to 200 µM against the different bacterial strains evaluated. Our results constitute relevant proven ML-workflow models to distinctively screen for novel MRSA antibiotics.

Could giant viruses be considered as a biotechnological tool for preventing and controlling Acanthamoeba infections?

AIM: The aim of the study was to evaluate the efficiency of mimivirus as a potential therapeutic and prophylactic tool against Acanthamoeba castellanii, the etiological agent of Acanthamoeba keratitis, a progressive corneal infection, that is commonly associated with the use of contact lenses and can lead to blindness if not properly treated. METHODS AND RESULTS: Mimivirus particles were tested in different multiplicity of infection, along with commercial multipurpose contact lenses' solutions, aiming to assess their ability to prevent encystment and excystment of A. castellanii. Solutions were evaluated for their amoebicidal potential and cytotoxicity in MDCK cells, as well as their effectiveness in preventing A. castellanii damage in Madin-Darby canine kidney (MDCK) cells. Results indicated that mimivirus was able to inhibit the formation of A. castellanii cysts, even in the presence of Neff encystment solution. Mimivirus also showed greater effectiveness in controlling A. castellanii excystment compared to commercial solutions. Additionally, mimivirus solution was more effective in preventing damage caused by A. castellanii, presented greater amoebicidal activity, and were less cytotoxic to MDCK cells than commercial MPS. CONCLUSIONS: Mimivirus demonstrates a greater ability to inhibit A. castellanii encystment and excystment compared to commercial multipurpose contact lens solutions. Additionally, mimivirus is less toxic to MDCK cells than those commercial solutions. New studies utilizing in vivo models will be crucial for confirming safety and efficacy parameters.

Aminopyrimidine Derivatives as Multiflavivirus Antiviral Compounds Identified from a Consensus Virtual Screening Approach.

Around three billion people are at risk of infection by the dengue virus (DENV) and potentially other flaviviruses. Worldwide outbreaks of DENV, Zika virus (ZIKV), and yellow fever virus (YFV), the lack of antiviral drugs, and limitations on vaccine usage emphasize the need for novel antiviral research. Here, we propose a consensus virtual screening approach to discover potential protease inhibitors (NS3pro) against different flavivirus. We employed an in silico combination of a hologram quantitative structure-activity relationship (HQSAR) model and molecular docking on characterized binding sites followed by molecular dynamics (MD) simulations, which filtered a data set of 7.6 million compounds to 2,775 hits. Lastly, docking and MD simulations selected six final potential NS3pro inhibitors with stable interactions along the simulations. Five compounds had their antiviral activity confirmed against ZIKV, YFV, DENV-2, and DENV-3 (ranging from 4.21 ± 0.14 to 37.51 ± 0.8 µM), displaying aggregator characteristics for enzymatic inhibition against ZIKV NS3pro (ranging from 28 ± 7 to 70 ± 7 µM). Taken together, the compounds identified in this approach may contribute to the design of promising candidates to treat different flavivirus infections.

New anti-SARS-CoV-2 aminoadamantane compounds as antiviral candidates for the treatment of COVID-19.

Here, the antiviral activity of aminoadamantane derivatives were evaluated against SARS-CoV-2. The compounds exhibited low cytotoxicity to Vero, HEK293 and CALU-3 cells up to a concentration of 1,000 µM. The inhibitory concentration (IC50) of aminoadamantane was 39.71 µM in Vero CCL-81 cells and the derivatives showed significantly lower IC50 values, especially for compounds 3F4 (0.32 µM), 3F5 (0.44 µM) and 3E10 (1.28 µM). Additionally, derivatives 3F5 and 3E10 statistically reduced the fluorescence intensity of SARS-CoV-2 protein S from Vero cells at 10 µM. Transmission microscopy confirmed the antiviral activity of the compounds, which reduced cytopathic effects induced by the virus, such as vacuolization, cytoplasmic projections, and the presence of myelin figures derived from cellular activation in the face of infection. Additionally, it was possible to observe a reduction of viral particles adhered to the cell membrane and inside several viral factories, especially after treatment with 3F4. Moreover, although docking analysis showed favorable interactions in the catalytic site of Cathepsin L, the enzymatic activity of this enzyme was not inhibited significantly in vitro. The new derivatives displayed lower predicted toxicities than aminoadamantane, which was observed for either rat or mouse models. Lastly, in vivo antiviral assays of aminoadamantane derivatives in BALB/cJ mice after challenge with the mouse-adapted strain of SARS-CoV-2, corroborated the robust antiviral activity of 3F4 derivative, which was higher than aminoadamantane and its other derivatives. Therefore, aminoadamantane derivatives show potential broad-spectrum antiviral activity, which may contribute to COVID-19 treatment in the face of emerging and re-emerging SARS-CoV-2 variants of concern.

Surface fibrils on the particles of nucleocytoviruses: A review.

The capsid has a central role in viruses' life cycle. Although one of its major functions is to protect the viral genome, the capsid may be composed of elements that, at some point, promote interaction with host cells and trigger infection. Considering the scenario of multiple origins of viruses along the viral evolution, a substantial number of capsid shapes, sizes, and symmetries have been described. In this context, capsids of giant viruses (GV) that infect protists have drawn the attention of the scientific community, especially in the last 20 years, specifically for having bacterial-like dimensions with hundreds of different proteins and exclusive features. For instance, the surface fibrils present on the mimivirus capsid are one of the most intriguing features of the known virosphere. They are 150-nm-long structures attached to a 450-nm capsid, resulting in a particle with a hairy appearance. Surface fibrils have also been described in the capsids of other nucleocytoviruses, although they may differ substantially among them. In this mini review for non-experts, we compile the most important available information on surface fibrils of nucleocytoviruses, discussing their putative functions, composition, length, organization, and origins.

Evaluating Known Zika Virus NS2B-NS3 Protease Inhibitor Scaffolds via In Silico Screening and Biochemical Assays.

The NS2B-NS3 protease (NS2B-NS3pro) is regarded as an interesting molecular target for drug design, discovery, and development because of its essential role in the Zika virus (ZIKV) cycle. Although no NS2B-NS3pro inhibitors have reached clinical trials, the employment of drug-like scaffolds can facilitate the screening process for new compounds. In this study, we performed a combination of ligand-based and structure-based in silico methods targeting two known non-peptide small-molecule scaffolds with micromolar inhibitory activity against ZIKV NS2B-NS3pro by a virtual screening (VS) of promising compounds. Based on these two scaffolds, we selected 13 compounds from an initial library of 509 compounds from ZINC15's similarity search. These compounds exhibited structural modifications that are distinct from previously known compounds yet keep pertinent features for binding. Despite promising outcomes from molecular docking and initial enzymatic assays against NS2B-NS3pro, confirmatory assays with a counter-screening enzyme revealed an artifactual inhibition of the assessed compounds. However, we report two compounds, 9 and 11, that exhibited antiviral properties at a concentration of 50 µM in cellular-based assays. Overall, this study provides valuable insights into the ongoing research on anti-ZIKV compounds to facilitate and improve the development of new inhibitors.

Elaboration and Characterization of Pereskia aculeate Miller Extracts Obtained from Multiple Ultrasound-Assisted Extraction Conditions.

Pereskia aculeata Miller, is an unconventional food plant native to South America. This study aimed to investigate the influence of different ultrasonic extraction times (10, 20, 30, and 40 min) on the phytochemical profile, antioxidant and antibacterial activities of ethanolic extracts obtained from lyophilized Pereskia aculeate Miller (ora-pro-nobis) leaves, an under-researched plant. Morphological structure and chemical group evaluations were also conducted for the lyophilized P. aculeate leaves. The different extraction times resulted in distinct phenolic content and Antioxidant Activity (ATT) values. Different extraction time conditions resulted in phenolic compound contents ranging from 2.07 to 2.60 mg EAG.g-1 of extract and different ATT values. The ATT evaluated by DPPH was significantly higher (from 61.20 to 70.20 µM of TE.g-1 of extract) in extraction times of 30 and 40 min, respectively. For ABTS, it varied between 6.38 and 10.24 µM of TE.g-1 of extract and 24.34 and 32.12 µM ferrous sulp.g-1 of extract. All of the obtained extracts inhibited the growth of Staphylococcus aureus, particularly the treatment employing 20 min of extraction at the highest dilution (1.56 mg.mL-1). Although liquid chromatography analyses showed that chlorogenic acid was the primary compound detected for all extracts, Paper Spray Mass Spectrometry (PS-MS) suggested the extracts contained 53 substances, such as organic, fatty, and phenolic acids, sugars, flavonoids, terpenes, phytosterols, and other components. The PS-MS proved to be a valuable technique to obtain the P. aculeate leaves extract chemical profile. It was observed that the freeze-drying process enhanced the conservation of morphological structures of P. aculeate leaves, as evidenced by scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) identified carboxyl functional groups and proteins between the 1000 and 1500 cm-1 bands in the P. aculeate leaves, thus favoring water interaction and contributing to gel formation. To the best of our knowledge, this is the first study to evaluate different times (10, 20, 30 and 40 min) for ultrasound extraction of P. aculeate leaves. The polyphenols improved extraction, and high antioxidant activity demonstrates the potential for applying P. aculeate leaves and their extract as functional ingredients or additives in the food and pharmaceutical industries.

Diversity of Surface Fibril Patterns in Mimivirus Isolates.

Among the most intriguing structural features in the known virosphere are mimivirus surface fibrils, proteinaceous filaments approximately 150 nm long, covering the mimivirus capsid surface. Fibrils are important to promote particle adhesion to host cells, triggering phagocytosis and cell infection. However, although mimiviruses are one of the most abundant viral entities in a plethora of biomes worldwide, there has been no comparative analysis on fibril organization and abundance among distinct mimivirus isolates. Here, we describe the isolation and characterization of Megavirus caiporensis, a novel lineage C mimivirus with surface fibrils organized as "clumps." This intriguing feature led us to expand our analyses to other mimivirus isolates. By employing a combined approach including electron microscopy, image processing, genomic sequencing, and viral prospection, we obtained evidence of at least three main patterns of surface fibrils that can be found in mimiviruses: (i) isolates containing particles with abundant fibrils, distributed homogeneously on the capsid surface; (ii) isolates with particles almost fibrilless; and (iii) isolates with particles containing fibrils in abundance, but organized as clumps, as observed in Megavirus caiporensis. A total of 15 mimivirus isolates were analyzed by microscopy, and their DNA polymerase subunit B genes were sequenced for phylogenetic analysis. We observed a unique match between evolutionarily-related viruses and their fibril profiles. Biological assays suggested that patterns of fibrils can influence viral entry in host cells. Our data contribute to the knowledge of mimivirus fibril organization and abundance, as well as raising questions on the evolution of those intriguing structures. IMPORTANCE Mimivirus fibrils are intriguing structures that have drawn attention since their discovery. Although still under investigation, the function of fibrils may be related to host cell adhesion. In this work, we isolated and characterized a new mimivirus, called Megavirus caiporensis, and we showed that mimivirus isolates can exhibit at least three different patterns related to fibril organization and abundance. In our study, evolutionarily-related viruses presented similar fibril profiles, and such fibrils may affect how those viruses trigger phagocytosis in amoebas. These data shed light on aspects of mimivirus particle morphology, virus-host interactions, and their evolution.

Ultrastructural analysis of monkeypox virus replication in Vero cells.

In early May 2022, the first worldwide monkeypox virus (MPXV) outbreak was reported, with different clinical aspects from previously studied human monkeypox infections. Despite monkeypox medical importance, much of its biological aspects remain to be further investigated. In the present work, we evaluated ultrastructural aspects of MPXV asynchronous infections in Vero cells by transmission electron microscopy (TEM). The viral strain was isolated from a male patient infected during the 2022 outbreak. TEM analysis showed: (i) adhered intracellular mature virus particles before entry of the host cell; (ii) a reorganization of the rough endoplasmic reticulum cisternae into the so-called "mini-nuclei" structure associated with genome replication; and (iii) noticeably different sites within the viral factory presenting granular or fibrillar aspects. We also observed viral crescents, different MPXV particle morphotypes, and cellular alterations induced by infection, such as changes in the cytoskeleton structure and multimembrane vesicles abundance. Taken together, to the best of our knowledge, these results revealed for the first-time ultrastructural aspects of different steps of the MPXV cycle.

Designing drugs when there is low data availability: one-shot learning and other approaches to face the issues of a long-term concern.

INTRODUCTION: Modern drug discovery is generally accessed by useful information from previous large databases or uncovering novel data. The lack of biological and/or chemical data tends to slow the development of scientific research and innovation. Here, approaches that may help provide solutions to generate or obtain enough relevant data or improve/accelerate existing methods within the last five years were reviewed. AREAS COVERED: One-shot learning (OSL) approaches, structural modeling, molecular docking, scoring function space (SFS), molecular dynamics (MD), and quantum mechanics (QM) may be used to amplify the amount of available data to drug design and discovery campaigns, presenting methods, their perspectives, and discussions to be employed in the near future. EXPERT OPINION: Recent works have successfully used these techniques to solve a range of issues in the face of data scarcity, including complex problems such as the challenging scenario of drug design aimed at intrinsically disordered proteins and the evaluation of potential adverse effects in a clinical scenario. These examples show that it is possible to improve and kickstart research from scarce available data to design and discover new potential drugs.

A Brief History of Giant Viruses' Studies in Brazilian Biomes.

Almost two decades after the isolation of the first amoebal giant viruses, indubitably the discovery of these entities has deeply affected the current scientific knowledge on the virosphere. Much has been uncovered since then: viruses can now acknowledge complex genomes and huge particle sizes, integrating remarkable evolutionary relationships that date as early as the emergence of life on the planet. This year, a decade has passed since the first studies on giant viruses in the Brazilian territory, and since then biomes of rare beauty and biodiversity (Amazon, Atlantic forest, Pantanal wetlands, Cerrado savannas) have been explored in the search for giant viruses. From those unique biomes, novel viral entities were found, revealing never before seen genomes and virion structures. To celebrate this, here we bring together the context, inspirations, and the major contributions of independent Brazilian research groups to summarize the accumulated knowledge about the diversity and the exceptionality of some of the giant viruses found in Brazil.

Machine learning techniques applied to the drug design and discovery of new antivirals: a brief look over the past decade.

Introduction: Drug design and discovery of new antivirals will always be extremely important in medicinal chemistry, taking into account known and new viral diseases that are yet to come. Although machine learning (ML) have shown to improve predictions on the biological potential of chemicals and accelerate the discovery of drugs over the past decade, new methods and their combinations have improved their performance and established promising perspectives regarding ML in the search for new antivirals.Areas covered: The authors consider some interesting areas that deal with different ML techniques applied to antivirals. Recent innovative studies on ML and antivirals were selected and analyzed in detail. Also, the authors provide a brief look at the past to the present to detect advances and bottlenecks in the area.Expert opinion: From classical ML techniques, it was possible to boost the searches for antivirals. However, from the emergence of new algorithms and the improvement in old approaches, promising results will be achieved every day, as we have observed in the case of SARS-CoV-2. Recent experience has shown that it is possible to use ML to discover new antiviral candidates from virtual screening and drug repurposing.

Knowing and combating the enemy: a brief review on SARS-CoV-2 and computational approaches applied to the discovery of drug candidates.

Since the emergence of the new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) at the end of December 2019 in China, and with the urge of the coronavirus disease 2019 (COVID-19) pandemic, there have been huge efforts of many research teams and governmental institutions worldwide to mitigate the current scenario. Reaching more than 1,377,000 deaths in the world and still with a growing number of infections, SARS-CoV-2 remains a critical issue for global health and economic systems, with an urgency for available therapeutic options. In this scenario, as drug repurposing and discovery remains a challenge, computer-aided drug design (CADD) approaches, including machine learning (ML) techniques, can be useful tools to the design and discovery of novel potential antiviral inhibitors against SARS-CoV-2. In this work, we describe and review the current knowledge on this virus and the pandemic, the latest strategies and computational approaches applied to search for treatment options, as well as the challenges to overcome COVID-19.

Himatanthus bracteatus stem extracts present anti-flavivirus activity while an isolated sesquiterpene glucoside present only anti-Zika virus activity in vitro.

The hexane and ethanol extracts from Himatanthus bracteatus (Apocynaceae) stems were evaluated for antiviral activity against Zika virus, yellow fever virus and dengue virus 2 and for cytotoxicity in Vero cells by MTT assay. The ethanol extract showed good antiviral activity against the three viruses with selective indexes (SI) > 10 and its fractionation led to the isolation of the known plumieride that was active only against Zika virus (SI of 15.97).

The application of machine learning techniques to innovative antibacterial discovery and development.

INTRODUCTION: After the initial wave of antibiotic discovery, few novel classes of antibiotics have emerged, with the latest dating back to the 1980's. Furthermore, the pace of antibiotic drug discovery is unable to keep up with the increasing prevalence of antibiotic drug resistance. However, the increasing amount of available data promotes the use of machine learning techniques (MLT) in drug discovery projects (e.g. construction of regression/classification models and ranking/virtual screening of compounds). AREAS COVERED: In this review, the authors cover some of the applications of MLT in medicinal chemistry, focusing on the development of new antibiotics, the prediction of resistance and its mechanisms. The aim of this review is to illustrate the main advantages and disadvantages and the major trends from studies over the past 5 years. EXPERT OPINION: The application of MLT to antibacterial drug discovery can aid the selection of new and potent lead compounds, with desirable pharmacokinetic and toxic profiles for further optimization. The increasing volume of available data along with the constant improvement in computational power and algorithms has meant that we are experiencing a transition in the way we face modern issues such as drug resistance, where our decisions are data-driven and experiments can be focused by data-suggested hypotheses.

Antibacterial activity of synthetic 1,3-bis(aryloxy)propan-2-amines against Gram-positive bacteria.

Synthetic 1,3-bis(aryloxy)propan-2-amines have been shown in previous studies to possess several biological activities, such as antifungal and antiprotozoal. In the present study, we describe the antibacterial activity of new synthetic 1,3-bis(aryloxy)propan-2-amines against Gram-positive pathogens (Streptococcus pyogenes, Enterococcus faecalis and Staphylococcus aureus) including Methicillin-resistant S. aureus strains. Our compounds showed minimal inhibitory concentrations (MIC) in the range of 2.5-10 µg/ml (5.99-28.58 µM), against different bacterial strains. The minimal bactericidal concentrations found were similar to MIC, suggesting a bactericidal mechanism of action of these compounds. Furthermore, possible molecular targets were suggested by chemical similarity search followed by docking approaches. Our compounds are similar to known ligands targeting the cell division protein FtsZ, Quinolone resistance protein norA and the Enoyl-[acyl-carrier-protein] reductase FabI. Taken together, our data show that synthetic 1,3-bis(aryloxy)propan-2-amines are active against Gram-positive bacteria, including multidrug-resistant strains and can be a promising lead in the development of new antibacterial compounds for the treatment of these infections.