New Highly Selective Antivirals for Chikungunya Virus identified from the Screening of a Drug-Like Compound Library.

Chikungunya fever is a mosquito-borne disease caused by Chikungunya virus (CHIKV). Treatment of CHIKV infections is currently supportive and does not limit viral replication or symptoms of persistent chronic arthritis. Although there are multiple compounds reported as antivirals active against CHIKV in vitro, there are still no effective and safe antivirals. Thus, active research aims at the identification of new chemical structures with antiviral activity. Here, we report the screen of the Pandemic Response Box library of small molecules against a fully infectious CHIKV reporter virus. Our screening approach successfully identified previously reported CHIKV antiviral compounds within this library and further expanded potentially active hits, supporting the use of reporter-virus-based assays in high-throughput screening format as a reliable tool for antiviral drug discovery. Four molecules were identified as potential drug candidates against CHIKV: MMV1634402 (Brilacidin) and MMV102270 (Diphyllin), which were previously shown to present broad-spectrum antiviral activities, in addition to MMV1578574 (Eravacycline), and the antifungal MMV689401 (Fluopicolide), for which their antiviral potential is uncovered here.

Characterization and Promising in vitro Antiherpetic Effect of Galactomannan from Delonix regia Seeds.

Herpes simplex virus (HSV) infections can occur throughout life, thereby allowing transmission to new hosts, with an impact on public health. Acyclovir remains the treatment of choice for these infections; however, an increase in resistant strains in recent years has been observed. In this study, the activity of a native Delonix regia galactomannan (NDr) against HSV-1 was investigated in vitro. NDr was characterized using infrared spectroscopy and NMR. Evaluation of cytotoxicity and the antiviral effect was determined, respectively, by MTT and plaque reduction assays. The NDr concentrations that inhibited cell viability (CC50) and viral infection (IC50) by 50% were above 2000 and 64 µg/mL, respectively. Thus, the polysaccharide showed a high selectivity index (> 31.25). When NDr was added at different stages of HSV-1 replication, a strong inhibitory effect was found by direct interaction with the virus (71-67%, virucidal effect) or previously with the cell, 6 h before infection (99.8-68.4%, prophylactic effect) at concentrations from 200 to 50 µg/mL. NDr showed similar effects in prophylactic 1 h (52%) and adsorption inhibition (55%) assays at 200 µg/mL. A reduction in the antiherpetic effect was observed after infection. These results suggest that NDr is effective in the early stages of HSV-1 infection and is a promising agent for controlling herpetic infections.

Liver biopsy-proven non-alcoholic fatty liver disease predicts no impact on antiviral response in patients with chronic hepatitis B.

OBJECTIVE: The role of Non-Alcoholic Fatty Liver Disease (NAFLD) on antiviral response in Chronic Hepatitis B (CHB) remains unclear. Previous studies mainly focus on the impact of the Non-Alcoholic Fatty Liver (NAFL) on antiviral efficacy, whereas the role of Non-Alcoholic Steatohepatitis (NASH) has not been highlighted. The authors aimed to investigate the association of NAFLD (NAFL and NASH), viral and histological characteristics with antiviral response. METHODS: The authors collected data of treatment-naïve CHB patients who underwent liver biopsy. All these patients received antiviral monotherapy and 48-week follow-up. The antiviral response was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the variables associated with antiviral response. RESULTS: Overall, 120 treatment-naïve CHB patients were enrolled, with 49.2 % (59/120) of them were complicated by NAFLD. Male (Odd Ratio [OR = 4.222], 95 % Confidence Interval [95 % CI 1.620-11.003]) and overweight (OR = 8.709, 95 % CI 3.355-22.606) were independent predictors for concurrent NAFLD. After 48-week follow-up, the authors found that the overall antiviral response did not differ between CHB patients with and without concomitant NAFL/NASH (p > 0.05). High viral load (Hazard Ratio [HR = 0.522], 95 % CI 0.286-0.952), advanced fibrosis (HR = 2.426, 95 % CI 1.256-4.686), and moderate-to-severe interface hepatitis (HR = 2.541, 95 % CI 1.406-4.592) were significantly correlated with antiviral response after 8-week follow-up. CONCLUSION: Neither NAFL nor NASH had an impact on antiviral therapy for CHB. It was low hepatitis B load, advanced fibrosis, and moderate-to-severe interface hepatitis that contributed to the virological response.

ß-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus.

Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic ß-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds 2b (83.33%) and 2d (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds 2b (EC50 = 18.92 µM; SI > 52.85), and 2d (EC50 = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC50 = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound 2b inhibited virus entry (62.64%). Also, compounds 2b and 2d inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.

Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C Shows Liver Fibrosis Regression on Three Noninvasive Tests: A Puerto Rican Cohort.

OBJECTIVE: Direct-acting antiviral (DAA) drugs have resulted in high rates of virological cure in chronic hepatitis C (CHC)-infected patients. We used noninvasive tests to assess fibrosis in subjects who had been cured with DAA. METHODS: Retrospective data collection (2014-2019) from the medical record of CHC patients at the hepatology clinic was performed. Subjects co-infected with HIV and hepatitis B, post-liver transplant, and lost to follow-up were excluded. We evaluated fibrosis at baseline and 1 year after completing therapy using vibration-controlled transient elastography (VCTE), fibrosis-4 (FIB-4), and aspartate aminotransferase-toplatelet ratio index (APRI) scores. RESULTS: With 210 medical records reviewed, 41 were included. The mean age was 62.8 years; 61% were men. Significant fibrosis regression was observed 1-year post-treatment using 3 noninvasive methods: VCTE, APRI, and FIB-4 score. Prior to treatment, 46% of the patients had advanced fibrosis compared to 25% 1 year after treatment. The VCTE scores of 4 subjects (with body mass indices [BMIs] > 30) indicated a worsening of fibrosis. We did not find a statistically significant association between BMI and VCTE, FIB-4, or APRI score. CONCLUSION: In most CHC patients, DAA therapy leads to liver fibrosis regression. Obesity may play an important role in the worsening of hepatic fibrosis or the absence of fibrosis regression.

Tackling a worrisome rate of lost to follow-up among migrants with hepatitis B in French Guiana.

OBJECTIVES: Management of Hepatitis B virus (HBV)-infected patients, whether they are receiving treatment or not, necessitates long-term follow-up. This study evaluated the rate of lost to follow-up (LTFU) among HBV-infected patients and the feasibility of a callback strategy to re-engage these patients in HBV care. PATIENTS AND METHODS: We conducted a retrospective study involving HBV-infected patients attending the outpatient clinic at Cayenne Hospital, French Guiana. LTFU was defined as patients who had not attended the clinic for more than 18 months. A callback strategy was implemented to re-engage LTFU patients in HBV care. RESULTS: Between 1st January 2015 and 31st December 2018, 203 HBV-infected patients were referred to the outpatient clinic; 95/203 (46.8 %) were LTFU, resulting in a crude LTFU rate of 2.6 (95 % CI, 2.1-3.2) per 100 person-years. At baseline, patients aged 30-40 years (aOR, 0.48; 95 %CI, 0.24-0.95) and those who initiated treatment (aOR, 0.26; 95 %CI, 0.10-0.60) were less likely to be LTFU. Through application of the callback strategy, 55/95 (58 %) patients were successfully contacted, and 46/55 (84 %) attended the outpatient clinic for a liver assessment. The EASL criteria for treatment eligibility were met by 3/46 (4 %) patients. Compared to non-LTFU patients, LTFU patients were more likely to be in informal employment (p = 0.03) and to be receiving state medical assistance (p < 0.01), and had lower levels of knowledge about their condition (p < 0.01). CONCLUSIONS: The callback strategy to re-engage LTFU patients in HBV care is feasible and effectively identifies those eligible for antiviral therapy.

Immunomodulatory markers and therapies for the management of infant respiratory syncytial virus infection.

INTRODUCTION: The human respiratory syncytial virus (hRSV) is one of childhood diseases' most common respiratory pathogens and is associated with lower respiratory tract infections. The peak in disease that this virus can elicit during outbreaks is often a significant burden for healthcare systems worldwide. Despite theapproval of treatments against hRSV, this pathogen remains one the most common causative agent of infant mortality around the world. AREAS COVERED: This review focuses on the key prognostic and immunomodulatory biomarkers associated with hRSV infection, as well as prophylactic monoclonal antibodies and vaccines. The goal is to catalyze a paradigm shift within the scientific community toward the discovery of novel targets to predict the clinical outcome of infected patients, as well as the development of novel antiviral agents targeting hRSV. The most pertinent research on this topic was systematically searched and analyzed using PubMed ISI Thomson Scientific databases. EXPERT OPINION: Despite advances in approved therapies against hRSV, it is crucial to continue researching to develop new therapies and to find specific biomarkers to predict the severity of infection. Along these lines, the use of multi-omics data, artificial intelligence and natural-derived compounds with antiviral activity could be evaluated to fight hRSV and develop methods for rapid diagnosis of severity.

Computational Screening to Predict MicroRNA Targets in the Flavivirus 3' UTR Genome: An Approach for Antiviral Development.

MicroRNAs (miRNAs) are molecules that influence messenger RNA (mRNA) expression levels by binding to the 3' untranslated region (3' UTR) of target genes. Host miRNAs can influence flavivirus replication, either by inducing changes in the host transcriptome or by directly binding to viral genomes. The 3' UTR of the flavivirus genome is a conserved region crucial for viral replication. Cells might exploit this well-preserved region by generating miRNAs that interact with it, ultimately impacting viral replication. Despite significant efforts to identify miRNAs capable of arresting viral replication, the potential of all these miRNAs to interact with the flavivirus 3' UTR is still poorly characterised. In this context, bioinformatic tools have been proposed as a fundamental part of accelerating the discovery of interactions between miRNAs and the 3' UTR of viral genomes. In this study, we performed a computational analysis to reveal potential miRNAs from human and mosquito species that bind to the 3' UTR of flaviviruses. In humans, miR-6842 and miR-661 were found, while in mosquitoes, miR-9-C, miR-2945-5p, miR-11924, miR-282-5p, and miR-79 were identified. These findings open new avenues for studying these miRNAs as antivirals against flavivirus infections.

Exploring the antiviral activities of the FDA-approved drug sulfadoxine and its derivatives against Chikungunya virus.

BACKGROUND: Currently, there is no antiviral licensed to treat chikungunya fever, a disease caused by the infection with Alphavirus chikungunya (CHIKV). Treatment is based on analgesic and anti-inflammatory drugs to relieve symptoms. Our study aimed to evaluate the antiviral activity of sulfadoxine (SFX), an FDA-approved drug, and its derivatives complexed with silver(I) (AgSFX), salicylaldehyde Schiff base (SFX-SL), and with both Ag and SL (AgSFX-SL) against CHIKV. METHODS: The anti-CHIKV activity of SFX and its derivatives was investigated using BHK-21 cells infected with CHIKV-nanoluc, a marker virus-carrying nanoluciferase reporter. Dose-response and time of drug-addition assays were performed in order to assess the antiviral effects of the compounds, as well as in silico data and ATR-FTIR analysis for insights on their mechanisms of action. RESULTS: The SFX inhibited 34% of CHIKV replication, while AgSFX, SFX-SL, and AgSFX-SL enhanced anti-CHIKV activity to 84%, 89%, and 95%, respectively. AgSFX, SFX-SL, and AgSFX-SL significantly decreased viral entry and post-entry to host cells, and the latter also protected cells against infection. Additionally, molecular docking calculations and ATR-FTIR analysis demonstrated interactions of SFX-SL, AgSFX, and AgSFX-SL with CHIKV. CONCLUSIONS: Collectively, our findings suggest that the addition of metal ions and/or Schiff base to SFX improved its antiviral activity against CHIKV.

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Electrospun nonwoven fabric of poly(ε-caprolactone)/n-phosphonium chitosan for antiviral applications: Fabrication, characterization, and potential efficacy.

This work reports the virucidal properties of nonwoven fibers developed via electrospinning with polycaprolactone (PCL) and chitosan quaternized with phosphonium salt (NPCS), emphasizing the influence of NPCS concentration on the structure of fibers and their performance against the MHV-3 coronavirus. The addition of NPCS enhances solutions conductivity and viscosity, leading to fibers containing a finer porous structure with a more hydrophilic and smoother surface, thereby making them a potent barrier against respiratory particles, which is a key factor for protective face masks. In terms of degradation, NPCS paced-up the process, suggesting potential environmental benefits. PCL/NPCS (90/10) fibers exhibit a 99 % coronavirus inhibition within a five-minute exposure without cellular toxicity, while also meeting breathability standards for medical masks. These findings suggest the use of NPCS as a promising strategy to design materials with remarkable virucidal performance and physical characteristics that reinforce their use in the field of biomaterials engineering.

Expanding Hepatitis C Virus Treatment in the New Mexico State Prison System: Using the ECHO Model for Provider and Prison Peer Education.

It is critical to address hepatitis C virus (HCV) in carceral settings to achieve worldwide elimination of the virus. We describe New Mexico's (NM) experience expanding HCV treatment in state prisons, supplemented with Project ECHO (ECHO; virtual mentorship through guided practice) and the NM Peer Education Program (NMPEP). We describe how using these programs may be a model for expanding treatment in prisons globally. ECHO, NM Corrections Department (NMCD) and Wexford Health Services (WHS) collaborate to treat HCV in state prisons and increase HCV knowledge among incarcerated persons using NMPEP. Each person arriving in prison is tested for HCV and those with active infection receive baseline labs, which are reviewed. Patients not meeting criteria for simplified treatment are presented to ECHO for expert guidance. Otherwise, patients are treated by WHS without consultation. NMPEP provides patient-to-patient education in prisons, addressing HCV myths and exploring treatment refusals. From December 2020 to June 2023, 3603 people had HCV viremia. In this study, 1685 people started treatment: 1280 were treated using the simplified algorithm and 405 were presented to ECHO. Of the 988 people who completed treatment and had sustained virologic response (SVR) labs drawn, 89.2% achieved SVR (i.e., cure). Most of the 107 people who did not achieve SVR had presumed reinfection. NMPEP trained 148 peer educators who educated 3832 peers about HCV prevention and treatment. HCV treatment in prisons can be expanded by implementing simplified treatment algorithms, use of the ECHO model for patients with advanced disease and peer education.

Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.

OBJECTIVE: In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects. METHODS: Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus. RESULTS: Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5µM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site. CONCLUSION: The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.

Antiviral Effect of Microalgae Phaeodactylum tricornutum Protein Hydrolysates against Dengue Virus Serotype 2.

Dengue, caused by the dengue virus (DENV), is a global health threat transmitted by Aedes mosquitoes, resulting in 400 million cases annually. The disease ranges from mild to severe, with potential progression to hemorrhagic dengue. Current research is focused on natural antivirals due to challenges in vector control. This study evaluates the antiviral potential of peptides derived from the microalgae Phaeodactylum tricornutum, known for its bioactive compounds. Microalgae were cultivated under controlled conditions, followed by protein extraction and hydrolysis to produce four peptide fractions. These fractions were assessed for cytotoxicity via the MTT assay and antiviral activity against DENV serotype 2 using flow cytometry and plaque formation assays. The 10-30 kDa peptide fraction, at 150 and 300 µg/mL concentrations, demonstrated no cytotoxicity and significantly reduced the percentage of infected cells and viral titers. These findings suggest that peptides derived from Phaeodactylum tricornutum exhibit promising antiviral activity against dengue virus serotype 2, potentially contributing to developing new therapeutic approaches for dengue.

Cytotoxic and Anti-HSV-1 Effects of Caulerpin Derivatives.

Marine organisms represent a potential source of secondary metabolites with various therapeutic properties. However, the pharmaceutical industry still needs to explore the algological resource. The species Caulerpa lamouroux Forssk presents confirmed biological activities associated with its major compound caulerpin, such as antinociceptive, spasmolytic, antiviral, antimicrobial, insecticidal, and cytotoxic. Considering that caulerpin is still limited, such as low solubility or chemical instability, it was subjected to a structural modifications test to establish which molecular regions could accept structural modification and to elucidate the cytotoxic bioactive structure in Vero cells (African green monkey kidney cells, Cercopithecus aethiops; ATCC, Manassas, VA, USA) and antiviral to Herpes simplex virus type 1. Substitution reactions in the N-indolic position with mono- and di-substituted alkyl, benzyl, allyl, propargyl, and ethyl acetate groups were performed, in addition to conversion to their acidic derivatives. The obtained analogs were submitted to cytotoxicity and antiviral activity screening against Herpes simplex virus type 1 by the tetrazolium microculture method. From the semi-synthesis, 14 analogs were obtained, and 12 are new. The cytotoxicity assay showed that caulerpin acid and N-ethyl-substituted acid presented cytotoxic concentrations referring to 50% of the maximum effect of 1035.0 µM and 1004.0 µM, respectively, values significantly higher than caulerpin. The antiviral screening of the analogs revealed that the N-substituted acids with methyl and ethyl groups inhibited Herpes simplex virus type 1-induced cytotoxicity by levels similar to the positive control acyclovir.

Synthesis, in vitro and in silico evaluation of gallamide and selenogallamide derivatives as inhibitors of the SARS-CoV-2 main protease.

The present work reports the inhibitory effect of amides derived from gallic acid (gallamides) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro), along with cytotoxicity evaluation and molecular docking studies. In addition to gallamides, other relevant compounds were also synthesized and evaluated against Mpro, making a total of 25 compounds. Eight compounds presented solubility issues during the inhibitory assay and one showed no inhibitory activity. Compounds 3a, 3b, and 3f showed the highest enzymatic inhibition with IC50 = 0.26 ± 0.19 µM, 0.80 ± 0.38 µM, and 2.87 ± 1.17 µM, respectively. Selenogallamide 6a exhibited IC50 values of 5.42 ± 2.89 µM and a comparison with its nonselenylated congener 3c shows that the insertion of the chalcogen moiety improved the inhibitory capacity of the compound by approximately 10 times. Regarding the cellular toxicity in THP-1 and Vero cells, compounds 3e and 3g, showed moderate cytotoxicity in Vero cells, while for THP-1 both were nontoxic, with CC50 > 150 µM. Derivative 3d showed moderate cytotoxicity against both cell lines, whereas 6d was moderatly toxic to THP-1. Other compounds analyzed do not induce substantial cellular toxicity at the concentrations tested. The molecular docking results for compounds 3a, 3b, and 3f show that hydrogen bonding interactions involving the hydroxyl groups (OH) of the gallate moiety are relevant, as well as the carbonyl group.

Characteristics and outcome of influenza-associated encephalopathy/encephalitis among children in China.

BACKGROUND: Influenza-Associated Encephalopathy/Encephalitis (IAE) is characterized by high incidence and poor prognosis. The aim of this study is to describe the clinical features and outcomes of IAE in pediatric patients. METHODS: We performed a retrospective review of hospitalized cases of laboratory-confirmed influenza infection between January 2018 and December 2021. Demographic, clinical, imaging, treatment and outcome data were collected. Statistical analysis was performed using SPSS software. RESULTS: Of 446 children hospitalized with influenza, 71 cases were identified with a diagnosis of IAE. The median age was 3 years and 46 (64.8 %) were younger than 5 years. Only one patient was vaccinated for seasonal influenza. 46 (64.8 %) patients had abnormal electroencephalogram examination and 47 (66.2 %) had abnormal brain MRI or CT findings. 68 (95.8 %) patients were treated with oseltamivir/peramivir. 12 (16.9 %) patients suffered mortality. Non-survivors were more likely to have lower Glasgow coma score (median 7), longer duration of fever (median 3 days), with underlying medical conditions (P = 0.006), and complications including sepsis (P = 0.003), shock (P < 0.001), respiratory failure (P = 0.006), acute renal failure (P = 0.001), myocardial damage (P < 0.001), coagulation disorders (P = 0.03), electrolyte disturbance (P = 0.001) and hyperlactacidemia (P = 0.003). Non-survivors had higher percentages of corticosteroids (P = 0.003) and immunoglobulin (P = 0.003) treatments compared to survivors. CONCLUSIONS: Children with IAE have a high mortality rate. Lower Glasgow coma score, longer duration of fever, with underlying medical conditions and complications pose a great risk to poor prognosis. Influenza vaccination is recommended to all eligible children.

Addressing corneal opacity after herpes zoster infection.

A 15-year-old boy was referred for corneal opacity evaluation. The patient had a previous herpes zoster virus (HZV) infection-varicella-zoster virus (VZV)-with ocular manifestation 1 year ago. After the infection, he developed a central corneal scar and decreased corrected distance visual acuity (CDVA) in the right eye. The slitlamp examination showed the right eye with central corneal opacity (involving anterior stroma), lacuna area between the haze, fluorescein negative, and no vascularization near the scar (Figure 1JOURNAL/jcrs/04.03/02158034-202406000-00019/figure1/v/2024-07-10T174224Z/r/image-tiff). The patient had been treated with oral valacyclovir and topical corticosteroids without any improvement of visual acuity or changes in opacity within the 1-year follow-up. His CDVA was 20/200 (-4.50 -0.75 × 25) in the right eye and counting fingers (-4.00) in the left eye. Intraocular pressure was 12 mm Hg in both eyes. Fundoscopy was normal in the right eye, but he had a macular scar in the left eye (diagnosed when he was 7 years). The left eye had no cornea signs. The patient has no comorbidity or previous surgeries. Considering this case, a corneal central scar in a 15-year-old boy, legally single eye only, and assuming it is an opacity in the anterior stroma, would you consider surgery for this patient? If so, which would you choose: Would you consider an excimer laser treatment of his ametropia while partially removing his opacity, a phototherapeutic keratectomy (PTK), or a PTK followed by a topography-guided treatment, femtosecond laser-assisted anterior lamellar keratoplasty (FALK), or deep anterior lamellar keratoplasty (DALK) or penetrating keratoplasty (depending on the scar depth)? Would you consider prophylactic acyclovir during and after surgery? Would you consider any other surgical step to prevent delayed corneal healing-persistent epithelial defect? Before the surgical approach, would you consider treating this patient with topical losartan (a transforming growth factor [TGF]-ß signaling inhibitor)? Would you first perform the surgery (which one) and then start the medication? Furthermore, if so, how long would you treat this patient? Would you consider treatment with another medication?