Piya Paul Mudgal

Hepatitis E represents an increasingly significant yet often overlooked public health issue in India, contributing substantially to both sporadic hepatitis cases and widespread waterborne outbreaks. Hepatitis E virus (HEV) is the foremost cause of acute viral hepatitis (AVH) in India and spreads primarily through contaminated water. Genotype-specific differences in transmission routes, ranging from enteric routes in developing regions to zoonotic routes in industrialized settings, underscore the complexity of its epidemiology. Vulnerable populations such as pregnant women, animal handlers, and immunocompromised individuals face a markedly increased risk of severe disease outcomes, including fulminant hepatic failure and chronic infection, in cases of coinfection with hepatitis B virus. This comprehensive review delves into Indian epidemiological trends, clinical features, diagnostic approaches, and current management options for HEV. While most infections are self-limiting, ribavirin has shown efficacy in select high-risk populations. However, the absence of an approved vaccine in India remains a critical gap in preventive strategies. Emerging therapeutics and vaccine candidates are currently in various stages of development. However, challenges such as the genetic diversity of HEVs, lack of long-term efficacy data, and limited public awareness hinder progress. This review emphasizes the urgent need for strengthened national surveillance systems, improved water and sanitation infrastructure, and integrated public health policies tailored for high-risk groups. A multipronged approach that combines epidemiological vigilance, clinical preparedness, and policy-driven interventions is imperative to halt the silent transmission of hepatitis E in India.

Chikungunya disease is spread by the bite of infected Aedes mosquitoes. It is considered a neglected tropical disease that has the potential to cause sporadic epidemics in naive populations. Despite the substantial investment in research, there are no approved antiviral treatments for chikungunya. Several screening approaches have been used to identify potential antiviral molecules that target the whole virus, viral proteins, and viral-host interactions, often in conjunction with computational studies. The genome of chikungunya virus (CHIKV) encodes four nonstructural and five structural proteins. The capsid protein (CP) is a small structural protein with enzymatic activity. Owing to its critical role in different stages of the viral life cycle, the CP can be targeted at multiple stages, thereby impeding viral multiplication. There is evidence suggesting that the CP may be a promising target for drug development, and this has led to the discovery of various inhibitors through diverse in vitro and in silico analyses. Both cell-based and cell-free assays have been widely used to identify and evaluate CHIKV CP inhibitors. Computer-based studies targeting CHIKV proteins, including CP, have identified several lead compounds, which are being further evaluated in various in vitro systems. No review has been published on the CHIKV CP, and papers have focused on drug development and the targeting of viral proteins and associated factors. In this review, we summarize the research that has been conducted on the CHIKV CP, including structural studies, antiviral research, and prospects for the use of the CP as an antiviral target.

Herpes simplex virus type 2 (HSV-2) treatment faces challenges due to antiviral resistance and systemic side effects of oral therapies. Local delivery of antiviral agents, such as tenofovir (TDF) and zinc acetate dihydrate (ZAD), may offer improved efficacy and reduced systemic toxicity. This study’s objective is to develop and evaluate local unit dose formulations of TDF and ZAD combination for local treatment of HSV-2 infection and exploring their individual and combinatory effects in vitro. The study involved the development of immediate-release film and pessary formulations containing TDF and ZAD. These formulations were characterized for physicochemical properties and in vitro drug release profiles. Cytotoxicity and antiviral activity assays were conducted to evaluate the individual and combinatory effects of TDF and ZAD. Film formulations released over 90% of the drugs within 1 h, and pessary formulations within 90 min, ensuring effective local drug delivery. ZAD showed moderate antiviral activity while TDF exhibited significant antiviral activity at non-cytotoxic concentrations. The combination of TDF and ZAD demonstrated synergistic effects in co-infection treatments, reducing the concentration required for 50% inhibition of HSV-2. Developed film and pessary formulations offer consistent and predictable local drug delivery, enhancing antiviral efficacy while minimizing systemic side effects. The combination of TDF and ZAD showed potential synergy against HSV-2, particularly in co-infection treatments. Further preclinical studies on pharmacokinetics, safety, and efficacy are necessary to advance these formulations toward clinical application.

Dengue is an emerging, mosquito-borne viral disease of international public health concern. Dengue is endemic in more than 100 countries across the world. However, there are no clinically approved antivirals for its cure. Drug repurposing proves to be an efficient alternative to conventional drug discovery approaches in this regard, as approved drugs with an established safety profile are tested for new indications, which circumvents several time-consuming experiments. In the present study, eight approved RNA-dependent RNA polymerase inhibitors of Hepatitis C virus were virtually screened against the Dengue virus polymerase protein, and their antiviral activity was assessed in vitro. Schrödinger software was used for in silico screening, where the compounds were passed through several hierarchical filters. Among the eight compounds, dasabuvir was finally selected for in vitro cytotoxicity and antiviral screening. Cytotoxicity profiling of dasabuvir in Vero cells revealed changes in cellular morphology, cell aggregation, and detachment at 50 μM. Based on these results, four noncytotoxic concentrations of dasabuvir (0.1, 0.25, 0.5, and 1 µM) were selected for antiviral screening against DENV-2 under three experimental conditions: pre-infection, co-infection, and post-infection treatment, by plaque reduction assay. Viral plaques were reduced significantly (p < 0.05) in the co-infection and post-infection treatment regimens; however, no reduction was observed in the pretreatment group. This indicated a possible interference of dasabuvir with NS5 RdRp, as seen from in silico interaction studies, translating into a reduction in virus plaques. Such studies reiterate the usefulness of drug repurposing as a viable strategy in antiviral drug discovery. Graphical Abstract In this drug repurposing study, dasabuvir, a known anti-hepatitis C drug, was selected through virtual screening and assessed for its anti-dengue activity.

Japanese encephalitis (JE) caused by the Japanese encephalitis virus (JEV) is one of Asia's most common viral encephalitis. JEV is a flavivirus, common in rural and sub-urban regions of Asian countries. Although only 1% of JEV-infected individuals develop JE, there is a 20–30% chance of death among these individuals and possible neurological sequelae post-infection. No licensed anti-JE drugs are currently available, despite extensive efforts to develop them. Literature search was performed using databases such as PubMed Central, Google Scholar, Wiley Online Library, etc. using keywords such as Japanese encephalitis virus, antiviral drugs, antiviral drug screening, antiviral drug targets, etc. From around 230 papers/abstracts and research reviews retrieved and reviewed for this study, approximately 180 most relevant and important ones have been cited. Different approaches in drug testing and various antiviral drug targets explored so far have been thoroughly searched from the literature and compiled, besides addressing the future perspectives of the antiviral drug development strategies. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent advancements in understanding the biology of infection and new drug targets have been promising improvements. Despite hindrances such as the unavailability of a proper drug delivery system or a treatment regimen irrespective of the stage of infection, several promising anti-JE candidate molecules are in different phases of clinical trials. Nonetheless, efficient therapy against JEV is expected to be achieved with drug combinations and a highly targeted drug delivery system soon. Graphical abstract