Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality—about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to in vitro and in vivo experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.

Next-generation sequencing (NGS) from SARS-CoV-2-positive swabs collected during the last months of 2022 revealed a large deletion spanning ORF7b and ORF8 (426 nt) in six patients infected with the BA.5.1 Omicron variant. This extensive genome loss removed a large part of these two genes, maintaining in frame the first 22 aminoacids of ORF7b and the last three aminoacids of ORF8. Interestingly, the deleted region was flanked by two small repeats, which were likely involved in the formation of a hairpin structure. Similar rearrangements, comparable in size and location to the deletion, were also identified in 15 sequences in the NCBI database. In this group, seven out of 15 cases from the USA and Switzerland presented both the BA.5.1 variant and the same 426 nucleotides deletion. It is noteworthy that three out of six cases were detected in patients with immunodeficiency, and it is conceivable that this clinical condition could promote the replication and selection of these mutations.

Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease’s symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV.

Magnusiomyces clavatus is an emerging opportunistic fungal pathogen associated with severe systemic infections in immunocompromised patients, mostly among those suffering from hematological malignancies. Despite the increasing clinical significance, genomic data for M. clavatus remain limited. In this study, we report the first chromosomal-level genome assembly of M. clavatus using hybrid sequencing with Illumina and Oxford Nanopore Technologies. Three clinical isolates obtained from ICU patients in Verona (Italy) were sequenced and analyzed. The M. clavatus genome was resolved into 4 nuclear chromosomes and 1 circular mitochondrial genome, with a total length of 17.6 Mb and with 4,065 predicted protein-coding genes. Comparative analyses revealed structural differences from its closely related species M. capitatus. Phylogenetic analysis of 40 strains assembled on the resolved genome identified a novel clade (D), distinct from the previously described clades A, B, and C. All isolates exhibited intrinsic resistance to echinocandins and fluconazole. Genetic analysis identified conserved mutations in the FKS1 hotspot region encoding 1,3-β-glucan synthase, mirroring resistance-associated substitutions in M. capitatus. Additionally, a putative cyp51 homolog was identified as a likely contributor to azole resistance, suggesting conserved resistance mechanisms across Magnusiomyces species. This study discloses a new chromosomal-level assembly for M. clavatus, providing a significant genomic framework. This resource could enhance the accuracy of diagnostic methods, enabling comparative genomics with closely related fungi and facilitating a deeper investigation into the mechanisms of antifungal resistance and pathogenicity of this rare but increasingly reported pathogen.

Next generation sequencing (NGS) from SARS-CoV-2-positive swabs collected during the last months of 2022 revealed a large deletion between ORF7b and ORF8 (426 nt) in six patients infected with the BA.5.1 Omicron variant. This extensive genome loss removed a large part of these two genes, maintaining in frame the first 22 aminoacids of ORF7b and the last 3 aminoacids of ORF8. Interestingly, the deleted region was flanked by 2 small repeats, likely involved in the formation of a hairpin structure. Similar rearrangements, comparable in size and location to the deletion, were also identified in 15 sequences in the NCBI database. In this group, 7 out of 15 cases from the USA and Switzerland presented both the BA.5.1 variant and the same 426 nuclotides deletion. It is noteworthy that 3 out of 6 cases were detected in patients with immunodeficiency and is conceivable that this clinical condition could promote the replication and selection of these mutations.

The availability of new technologies for deep sequencing, including next-generation sequencing (NGS), allows for the detection of viral genome variations. The epidemiological determination of SARS-CoV-2 viral genome changes during the pandemic waves displayed the genome evolution and subsequent onset of variants over time. These variants were often associated with a different impact on viral transmission and disease severity. We investigated, in a retrospective study, the trend of SARS-CoV-2-positive samples collected from the start of the Italian pandemic (January 2020) to June 2023. In addition, viral RNAs extracted from 938 nasopharyngeal swab samples were analyzed using NGS between February 2022 and June 2023. Sequences were analyzed with bioinformatic tools to identify lineages and mutations and for phylogenetic studies. Six pandemic waves were detected. In our samples, we predominantly detected BA.2, BQ.1, BA.5.1, BA.5.2, and, more recently, XBB.1 and its subvariants. The data describe the SARS-CoV-2 genome evolution involved in viral interactions with the host and the dynamics of specific genome mutations and deletions.