The efficiency of human immunodeficiency virus-1 (HIV-1) inhibition by sulfated polysaccharides isolated from the various families of red algae of the Far East Pacific coast were studied. The anti-HIV-1 activity of kappa and lambda-carrageenans from Chondrus armatus, original highly sulfated X-carrageenan with low content of 3,6-anhydrogalactose from Tichocarpus crinitus and i/κ-carrageenan with hybrid structure isolated from Ahnfeltiopsis flabelliformis was found. The antiviral action of these polysaccharides and its low-weight oligosaccharide was compared with commercial κ-carrageenan. Here we used the HIV-1-based lentiviral particles and evaluated that these carrageenans in non-toxic concentrations significantly suppress the transduction potential of lentiviral particles pseudotyped with different envelope proteins, targeting cells of neuronal or T-cell origin. The antiviral action of these carrageenans was confirmed using the chimeric replication competent Mo-MuLV (Moloney murine leukemia retrovirus) encoding marker eGFP protein. We found that X-carrageenans from T. crinitus and its low weight derivative and λ-carrageenan from C. armatus effectively suppress the infection caused by retrovirus. The obtained data suggest that the differences in the suppressive effect of carrageenans on the transduction efficiency of HIV-1 based lentiviral particles may be related to the structural features of the studied polysaccharides.

This single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1-3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6-17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413-575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138-401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.

In severe stages of periodontitis, conventional periodontal therapy and maintenance care are usually insufficient due to the viral and bacterial etiology; thus, a mechanical approach alone may not be sufficient to eliminate a substantial portion of subgingival pathogens, especially in deep periodontal sites. Background and Objectives: This single-blind, randomized clinical trial aimed to compare the clinical and microbiological efficacy of a low-cost protocol using povidone-iodine and sodium hypochlorite formulations as adjuncts to non-surgical therapy for patients with stage IV periodontitis when compared with chlorhexidine, the most commonly employed substance to date for antimicrobial regimens in periodontal therapy. Materials and Methods: Forty-five patients were randomly divided into two groups: control (subgingival instrumentation, chlorhexidine-assisted) and test (antiviral medication, subgingival instrumentation with povidone-iodine, sodium hypochlorite rinsing solution, and antibiotics). Clinical measurements and microbiological analyses were performed at baseline and after three months. Results: After three months, notable differences were found in the bacterial detection scores for Porphyromonas gingivalis (a significant reduction in detection frequency was observed in the test compared to the control (p = 0.021)), and there were significant reductions in detection in the test group for Tannerella forsythia and Treponema denticola, showing undetectable levels (p < 0.0001 for both). In the test group, the pocket probing depth median value was reduced significantly (p = 0.0005); similarly, bleeding on probing showed a marked decrease (p < 0.0001). However, changes in clinical attachment loss and full-mouth plaque score were not statistically significant. Conclusions: Using the proposed protocol, substantial improvements in clinical and microbiological parameters were obtained when compared with the current antimicrobial recommendations.

We conducted a monocentric observational study aimed at evaluating the vaccine safety and the pharmaceutical service provided at a community pharmacy (C.PHARM) in the Puglia Region in the period from 29 December 2021 to 12 March 2022 using data from 550 patients of various ages and sexes and with concomitant diseases. We collected anamnestic data, the number of hospitalizations, and any post-vaccination adverse reactions. Interviews using the integrated EQ5 method were also performed to evaluate the quality of the service offered and any therapy preference. As expected, the vaccines were reactogenic after the first dose in the patients with mild-moderate reactions, with younger age and female gender as risk factors. Immune-allergic reactions of a moderate-severe degree were observed in adult females. In the elderly, the vaccination was well tolerated. Comirnaty® showed a favorable O.R. < 1 vs. other vaccines. No cardiovascular events or hospitalizations were observed up to May 2023. Regional data indicate that all treatments during May 2023 were correlated with the viremia. PaxlovidTM was prescribed in 3% of the patients in our center and in 1.46% in the region, and distributed/dispensed on behalf of third parties in accordance with a novel distribution/dispensation protocol of the C.PHARM that resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

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In recent years, the scientific community has worked intensively in the search and development of new drugs to suppress viral infections, such as COVID-19. In fact, a number of active compounds have been tested; however, the absence of significant structure-activity relationships hinders the production of optimized drugs. In this study, molecular modeling techniques were employed to investigate the electronic, structural and chemical reactivity properties of a set α-ketoamides whose antiviral activities have been reported in the literature, aiming to propose new promising derivatives. The local reactivity of the compounds was evaluated via condensed-to-atoms Fukui indexes and molecular electrostatic potential. Multivariate data analysis and random forests machine learning techniques were employed to correlate the antiviral properties and electronic and structural descriptors and identify relevant variables. A series of new derivatives were then proposed and evaluated via density functional theory-based calculations, and docking/molecular dynamics with the target protein of the virus. The results suggest that active derivatives present reduced reactivity towards electrophilic agents on the central core of the molecules and high reactivity on R1 ligands. Derivatives with higher predicted antiviral activities were proposed based on simple electronic descriptors, and their efficacies are reinforced by docking and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.

UNASSIGNED: Recurring viral outbreaks have a significant negative impact on society. This creates a need to develop novel strategies to complement the existing antiviral approaches. There is a need for safe and sustainable antiviral solutions derived from nature.
UNASSIGNED: This study aimed to investigate the antiviral potential of willow (Salix spp.) bark hot water extracts against coronaviruses and enteroviruses. Willow bark has long been recognized for its medicinal properties and has been used in traditional medicines. However, its potential as a broad-spectrum antiviral agent remains relatively unexplored.
UNASSIGNED: Cytopathic effect inhibition assay and virucidal and qPCR-based assays were used to evaluate the antiviral potential of the bark extracts. The mechanism of action was investigated using time-of-addition assay, confocal microscopy, TEM, thermal, and binding assays. Extracts were fractionated and screened for their chemical composition using high-resolution LC-MS.
UNASSIGNED: The native Salix samples demonstrated their excellent antiviral potential against the non-enveloped enteroviruses even at room temperature and after 45 s. They were equally effective against the seasonal and pandemic coronaviruses. Confocal microscopy verified the loss of infection capacity by negligible staining of the newly synthesized capsid or spike proteins. Time-of-addition studies demonstrated that Salix bark extract had a direct effect on the virus particles but not through cellular targets. Negative stain TEM and thermal assay showed that antiviral action on enteroviruses was based on the added stability of the virions. In contrast, Salix bark extract caused visible changes in the coronavirus structure, which was demonstrated by the negative stain TEM. However, the binding to the cells was not affected, as verified by the qPCR study. Furthermore, coronavirus accumulated in the cellular endosomes and did not proceed after this stage, based on the confocal studies. None of the tested commercial reference samples, such as salicin, salicylic acid, picein, and triandrin, had any antiviral activity. Fractionation of the extract and subsequent MS analysis revealed that most of the separated fractions were very effective against enteroviruses and contained several different chemical groups such as hydroxycinnamic acid derivatives, flavonoids, and procyanidins.
UNASSIGNED: Salix spp. bark extracts contain several virucidal agents that are likely to act synergistically and directly on the viruses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19) has spread pandemically with high rates of morbidity and mortality. COVID-19 has also posed unprecedented challenges in terms of rapid development of pharmacological countermeasures to prevent or contrast SARS-CoV-2 pathogenicity. Anti-SARS-CoV-2 antiviral agents and monoclonal antibodies have been specifically designed to attenuate COVID-19 morbidity and prevent mortality in vulnerable subjects, such as patients with immune-mediated diseases, but evidence for the safe and effective use of these drugs in this latter population group is scarce. Therefore, we designed a retrospective, multicentre, observational, case-control study to analyse the impact of these treatments in COVID-19 patients with systemic lupus erythematosus (SLE), a paradigmatic, multi-organ autoimmune disease. We identified 21 subjects treated with antivirals and/or monoclonal antibodies who were matched with 42 untreated patients by age, sex, SLE extension and duration. Treated patients had higher baseline SLE disease activity index 2000 scores [SLEDAI-2K median (interquartile range) = 4 (1-5) vs. 0 (0-2); p = 0.009], higher prednisone doses [5 (0-10) mg vs. 0 (0-3) mg; p = 0.002], and more severe COVID-19 symptoms by a five-point World Health Organisation-endorsed analogue scale [1 (0-1) vs. 0 (0-1); p < 0.010] compared to untreated patients. There was no difference between groups in terms of COVID-19 outcomes and sequelae, nor in terms of post-COVID-19 SLE exacerbations. Three subjects reported mild adverse events (two with monoclonal antibodies, one with nirmatrelvir/ritonavir). These data suggest that anti-SARS-CoV-2 antivirals and monoclonal antibodies might be safely and effectively used in patients with SLE, especially with active disease and more severe COVID-19 symptoms at presentation.

Coronavirus disease 2019 (COVID-19) caused a progress in research to find a solution to this pandemic. Also, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, casirivimab and imdevimab are antibodies combination against COVID-19. Standard antiviral therapy against COVID-19 includes remdesivir and favipiravir. The objectives were to compare progression and multi-organ function of hospitalized COVID-19 patients between these three antiviral groups. 265 COVID-19 hospitalized patients were included in this study and were divided into 3 groups (1:2:2), respectively, Group (A): casirivimab and imdevimab, group (B): remdesivir, and group (C): favipiravir. The design of the study is a single blind non-randomized controlled trial. This study is a phase IV clinical trial (post-marketing study). The duration of the study was about 6 months after receiving the ethical approval. Casirivimab and imdevimab achieved less case progression as presented by lower World Health Organization scale (P < 0.05 in comparing group A with B and C) and better multi-organ functions as presented by lower Sequential Organ Function Assessment score (P < 0.05 in comparing group A with B and C) than remdesivir and favipiravir. From all these results, it is concluded that Group A (casirivimab and imdevimab) produces better outcomes than B (remdesivir) and C (favipiravir) intervention groups.

OBJECTIVE: To estimate the prevalence of potential moderate to severe drug-drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs.
METHODS: Cross-sectional study.
METHODS: Electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID-19 data resources in the United States.
METHODS: Outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022.
METHODS: Nirmatrelvir/ritonavir.
METHODS: The outcome is potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir.
RESULTS: Of 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8 ± 17.1 years, 39.5% were male, and 65.8% were non-Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10-year increase, 95% confidence interval [CI] 1.08-1.25), male (OR 1.36, CI 1.09-1.71), smokers (OR 1.38, CI 1.10-1.73), on more co-medications (OR 1.35, CI 1.31-1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05-6.45).
CONCLUSIONS: One in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks.