Carmaphycin B-Based Proteasome Inhibitors to Treat Human African Trypanosomiasis: Structure-Activity Relationship and Efficacy.

The proteasome is essential for eukaryotic cell proteostasis, and inhibitors of the 20S proteasome are progressing preclinically and clinically as antiparasitics. We screened, the causative agent of human and animal African trypanosomiasis, with a set of 27 carmaphycin B analogs, irreversible epoxyketone inhibitors that were originally developed to inhibit the20S (Pf20S). The structure-activity relationship was distinct from that of the human c20S antitarget by the acceptance of d-amino acids at the P3 position of the peptidyl backbone to yield compounds with greatly decreased toxicity to human cells.

Structure elucidation, biosynthetic gene cluster distribution, and biological activities of ketomemicin analogs in .

We report three new ketomemicin pseudopeptides (-) from extracts of the marine actinomycete strain CNY-498. Their constitution and relative configuration were elucidated using NMR, mass spectrometry, and quantum chemical calculations. Using GNPS molecular networking and publicly available LCMS datasets, five additional ketomemicin analogs (-) were identified with ketomemicin production detected broadly across species.

Development of an Antiviral Medicinal Plant and Natural Product Database (avMpNp Database) from Biodiversity.

The construction of compound databases (DB) is a strategy for the rational search of bioactive compounds and drugs for new and old diseases. In order to bring greater impact to drug discovery, we propose the development of a DB of bioactive antiviral compounds. Several research groups have presented evidence of the antiviral activity of medicinal plants and compounds isolated from these plants.

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.

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.

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 (NS3) against different flavivirus.

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 (IC) of aminoadamantane was 39.

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.

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.

Activation mechanism and activity of globupain, a thermostable C11 protease from the Arctic Mid-Ocean Ridge hydrothermal system.

Deep-sea hydrothermal vents offer unique habitats for heat tolerant enzymes with potential new enzymatic properties. Here, we present the novel C11 protease , which was prospected from a metagenome-assembled genome of uncultivated sampled from the Soria Moria hydrothermal vent system located on the Arctic Mid-Ocean Ridge. Sequence comparisons against the MEROPS-MPRO database showed that globupain has the highest sequence identity to C11-like proteases present in human gut and intestinal bacteria.

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

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 Miller (ora-pro-nobis) leaves, an under-researched plant. Morphological structure and chemical group evaluations were also conducted for the lyophilized leaves.

Activation mechanism and activity of globupain, a thermostable C11 protease from the Arctic Mid-Ocean Ridge hydrothermal system.

Deep-sea hydrothermal vent systems with prevailing extreme thermal conditions for life offer unique habitats to source heat tolearant enzymes with potential new enzymatic properties. Here, we present the novel C11 protease , prospected from a metagenome-assembled genome of uncultivated sampled from the Soria Moria hydrothermal vent system located on the Arctic Mid- Ocean Ridges. By sequence comparisons against the MEROPS-MPRO database, globupain showed highest sequence identity to C11-like proteases present in human gut and intestinal bacteria,.

Development of subunit selective substrates for proteasome.

The protozoan parasite, (Tv) causes trichomoniasis, the most common, non-viral, sexually transmitted infection in the world. Only two closely related drugs are approved for its treatment. The accelerating emergence of resistance to these drugs and lack of alternative treatment options poses an increasing threat to public health.

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.

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).

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.

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.

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

: 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.: The authors consider some interesting areas that deal with different ML techniques applied to antivirals.

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.

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 (.

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

The hexane and ethanol extracts from (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).

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.