Recent Advances in Anti-Infective Drug Discovery - Current Issue

The human microbiome plays a pivotal role in health and disease, with microbial imbalances (dysbiosis) increasingly linked to heightened susceptibility to infections and exacerbated disease severity. This review explores how the microbiome confers protection through mechanisms, such as colonization resistance, immune modulation, and antimicrobial metabolite production, while also examining its potential as a predictive tool for infection risk and outcomes, as exemplified in COVID-19.

This article synthesizes current literature on microbiome dynamics, leveraging advances in high-throughput sequencing, bioinformatics, and machine learning to analyze microbial profiles and identify biomarkers. It evaluates microbiome-based therapeutic strategies, including probiotics, prebiotics, and engineered microbes, and assesses challenges in translating these approaches into clinical practice.

Microbiome profiles demonstrate prognostic value in predicting infection risk and severity, supported by enhanced analytical tools that enable precise biomarker discovery for diagnostics and personalized medicine. Therapeutic interventions show promise in restoring microbial balance and combating infections, though clinical adoption is hindered by variability, regulatory hurdles, and the need for standardized methodologies.

Integrating microbiome insights into clinical practice requires rigorous clinical trials, standardized protocols, and resolution of ethical and regulatory challenges. Future research should focus on elucidating microbiome-host-pathogen interactions and developing targeted interventions, and advanced computational models are critical to unlocking the full potential of microbiome-based diagnostics and therapeutics for infectious disease management.

Viral infections continue to be a major global health issue, causing over five million fatalities and millions of hospitalizations every year. Existing vaccines and commonly used antiviral drugs often exhibit significant side effects and limited efficacy. In contrast, recent studies have shown that plant extracts and their bioactive compounds possess considerable antiviral activity, along with a favourable safety profile for long-term use. These findings have spurred increased interest in the discovery and development of novel plant-derived antiviral agents.

This review emphasizes the significance of plant-derived antiviral compounds and their corresponding therapeutic targets. It provides a comprehensive overview of recent research on phytochemicals with potential antiviral activity against a wide range of viruses. By consolidating current findings, this review serves as a unified and up-to-date resource on contemporary plant-based antiviral bioactive compounds used in the treatment of human viral infections.

The antiviral efficacy of selected phytoactive compounds was analysed through detailed molecular mechanism studies, supported by in vitro and/or in vivo experimental models. Key herbs were reviewed for their active compounds and antiviral activities against specific viruses like influenza, HIV, HBV, HCV, HSV SARS-CoV-2, and measles. The study also analyzed the results, comparing their mechanisms of action, such as immune modulation, inhibition of viral entry, or interference with replication, while also discussing limitations and gaps in current research.

Evidence from the literature suggests that the notable selectivity of herbal bioactive compounds toward viral target proteins may underlie their antiviral activity. Additionally, findings from in silico, in vitro, and in vivo studies indicate that these compounds exert their effects by binding to specific host cell components, thereby protecting the host from viral infection. This review identifies and summarizes over 150 plant-derived antiviral bioactive compounds, along with their respective mechanisms of action, that have demonstrated efficacy against various selected viruses.

Plant-derived compounds, such as alkaloids, flavonoids, phenolics, terpenoids, and coumarins, exhibit significant antiviral potential. Given the limited number of approved antiviral drugs, cellular and molecular evidence supports herbal bioactives as promising alternatives for developing effective antiviral therapies, offering a natural and safer approach to combating viral infections.

The recent COVID-19 wave showed a significant rise in mucormycosis, changing its prevalence, particularly in India. Sadly, the total risk of mortality due to COVID-19 associated mucormycosis (CAM) remains high. It may be better to introduce a combination of drugs rather than unacceptable poor outcomes with Amphotericin B monotherapy.

The aim of this study is to assess the proportion of mucormycosis patient’s clinical outcomes with antifungal agent (Amphotericin B of any forms alone) or combination drug therapy (Amphotericin B of any form and Posaconazole).

It was a retrospective cohort study conducted between April 1^st, 2021 and July 31^st, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur.

Out of 271 medical records of CAM patients, 211 records were included in the study. Among them, 46 patients (21.8%) received group 1 treatment i.e. Amphotericin only and 165 patients (78.2%) received group 2 treatment, i.e. Amphotericin B with Posaconazole. Group 2 was associated with a longer time to event, having a higher survival rate. The Hazard Ratio (HR) was 0.22 (95% CI – 0.13-0.36, p-value 0.000).

Our findings will support the need for future studies to determine the efficacy of AMB and posaconazole combination therapy in the treatment of mucormycosis and to produce an evidence-based standard treatment regimen.

Fever of Unknown Origin (FUO) was first defined in 1961 as a temperature greater than 38.3°C on several occasions, lasting for more than 3 weeks, or failure to reach a diagnosis despite one week of inpatient investigation. The time frame has recently been revised to include patients whose illness remains undiagnosed after either a minimum of three outpatient visits or three days of hospitalization. The purpose of this study was to describe the etiology, frequency, and pattern of different causes, particularly infectious causes, and to determine the relative incidence of various causes of FUO in the mid-Delta area of Egypt.

This retrospective cohort study included all FUO cases registered in the file system over a seven-year period from 2015 to 2022 at Mahala-Kubra Fever Hospital, as well as all admitted FUO cases at the Tropical Medicine and Infectious Diseases Department of Tanta University during 2021 and 2022.

A total of 383 FUO cases were included in the study. Among these, the leading causes of FUO were infections (n = 334, 87.2%), followed by neoplasms (n = 26, 6.8%). Autoimmune and miscellaneous causes ranked third (n = 9, 2.3%), and undiagnosed cases were the least common (n = 5, 1.3%). The two most common infectious causes in this study were urinary tract infection (n = 136, 40.7%) and brucellosis (n = 115, 34.4%). Typhoid fever (n = 29, 8.7%), pneumonia (n = 15, 4.2%), and abscesses (n = 10, 3.0%) were also frequent causes of FUO. Hematological malignancies were the most common malignant causes of FUO, with lymphoma being the most prevalent (n = 10, 38.5%), followed by leukemia (n = 8, 30.8%).

Fever (pyrexia) of unknown origin remains one of the most challenging complexities in medical diagnosis. Infections, particularly Urinary Tract Infections (UTIs) and brucellosis, are the primary causes of FUO in this study. It is also important to recognize that hematological malignancies are a significant cause of FUO.