Viruses represent the most common cause of infectious diseases worldwide and those with rapid propagation and high infection rates cause human and animal pandemics. These fast-spreading diseases are generally treated with antiviral drugs but, often, drug resistance occurs because of the ability of the pathogens to mutate rapidly and become less susceptible to the treatments. Even though new antivirals have been approved, e.g., in HIV (human immunodeficiency virus) and HCV (hepatitis C virus) therapeutic areas, the need to dispose of new pharmaceutical tools for the management of infections that still have no treatment is of growing interest. In these areas, carbazole represents an important privileged scaffold in drug discovery. Many compounds with a carbazolic core have been developed and some of them have shown antiviral activity. This review provides an overview on some already known carbazole derivatives, pointing the attention on the running progresses in identifying new molecules with carbazolic structure, that have shown interesting and encouraging in vitro and in vivo properties. These drugs may be exploited as valid alternatives in antiviral therapy.

Background and objectives: To enter the target cell, HIV-1 binds not only CD4 but also a co-receptor β-chemokine receptor 5 (CCR5) or α chemokine receptor 4 (CXCR4). Limited information is available on the impact of co-receptor usage on HIV-1 replication in monocyte-derived macrophages (MDM) and on the homeostasis of this important cellular reservoir. Materials and Methods: Replication (measured by p24 production) of the CCR5-tropic 81A strain increased up to 10 days post-infection and then reached a plateau. Conversely, the replication of the CXCR4-tropic NL4.3 strain (after an initial increase up to day 7) underwent a drastic decrease becoming almost undetectable after 10 days post-infection. The ability of CCR5-tropic and CXCR4-tropic strains to induce cell death in MDM was then evaluated. While for CCR5-tropic 81A the rate of apoptosis in MDM was comparable to uninfected MDM, the infection of CXCR4-tropic NL4.3 in MDM was associated with a rate of 14.3% of apoptotic cells at day 6 reaching a peak of 43.5% at day 10 post-infection. Results: This suggests that the decrease in CXCR4-tropic strain replication in MDM can be due to their ability to induce cell death in MDM. The increase in apoptosis was paralleled with a 2-fold increase in the phosphorylated form of p38 compared to WT. Furthermore, microarray analysis showed modulation of proapoptotic and cancer-related genes induced by CXCR4-tropic strains starting from 24 h after infection, whereas CCR5 viruses modulated the expression of genes not correlated with apoptotic-pathways. Conclusions: In conclusion, CXCR4-tropic strains can induce a remarkable depletion of MDM. Conversely, MDM can represent an important cellular reservoir for CCR5-tropic strains supporting the role of CCR5-usage in HIV-1 pathogenesis and as a pharmacological target to contribute to an HIV-1 cure.

Although analysis of the Human papillomavirus (HPV) genotype spread in a particular area has a crucial impact on public health and prevention programmes, there is a lack of epidemiological data regarding HPV in the Calabria region of Italy. We therefore update information on HPV age/genotype distribution by retrospectively analysing a cohort of women, with and without cervical lesions, living in Calabria, who underwent HPV DNA testing; moreover, we also evaluated HPV age/genotype distribution in a subset of patients with cervical lesions. Cervical scrape specimens obtained from 9590 women (age range 20–75 years) from January 2010 to December 2015 were tested for HPV DNA. Viral types were genotyped by Linear Array HPV Genotyping® test (Roche, USA) at the Clinical Microbiology Operative Unit of six hospitals located in four provinces of the Calabria region. Cervical scrape specimens were also used to perform Pap smears for cytological analysis in a subset of 405 women; cytological classification of the samples was performed according to the Bethesda classification system. A total of 2974 women (31%) (C.I. 95% 30.09–31.94) were found to be HPV DNA positive for at least one (57.3%) or several (42.7%) HPV genotypes. Of single genotype HPV infections, 46.5% and 36.4 % were classed as high-risk (HR, Group 1) and low-risk (LR, Group 3) respectively, while 16.9% were classed as probably/possibly carcinogenic and 0.2% undetermined risk. Stratified by age, total HPV distribution, showed the highest prevalence within the range 30–39 years (37.2%), while single genotype infection distribution displayed a peak in women from the age range 20–29 years (37.5%). The most common high-risk HPV type was HPV 16 (19.1%), followed by HPV 31 (9.1%). We provide epidemiological data on HPV age/genotype distribution in women living in the Calabria region with or without cytological abnormalities, further to the enhancement of HPV screening/prevention programmes for the local population.

Mastroianni A, et al. Infect Chemother. 2022 Mar;54:e16. https://doi.org/10.3947/ic.2021.0070