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    Tackling cutaneous herpes simplex virus disease with topical immunomodulators—a call to action
    (American Society for Microbiology, 2025-03-13)
    DUARTE PEÑALOZA, LUISA FERNANDA  
    ;
    Javier Carbone-Schellman
    ;
    Susan M. Bueno
    ;
    Alexis M. Kalergis
    ;
    Claudia A. Riedel
    Antivirals play important roles in restricting viral diseases. Nevertheless, they act on a relatively limited number of viruses and occasionally display partial effectiveness in some tissues or against escape variants. Although vaccination remains the most cost-effective approach for preventing microbial diseases, developing prophylactic or therapeutic solutions for pathogens, such as herpes simplex viruses (HSVs), that effectively reduce their clinical manifestations in the skin has proven exceptionally challenging despite extensive research. Alternatively, a less explored approach for tackling HSV skin infection involves using topical immunomodulatory molecules to potentiate the host’s innate antiviral immune responses. When applied directly to herpetic skin lesions where viral antigen is present, this strategy has the potential to elicit virus-specific adaptive immunity. Based on currently available data, we foresee substantial potential for this approach in addressing HSV skin infections, along with additional prospects to advance understanding of skin biology and apply relevant new findings to other dermatological conditions. However, due to the limited number of case studies evaluating this method and its safety profile, particularly in immunocompromised individuals and pregnant women, further research is crucial, especially to assess the effects of immunomodulators in these vulnerable populations. Here, we revisit and discuss the use of immunomodulatory molecules for potentiating the host immune response against HSV skin infection and call for action for increased research and clinical trials regarding the possible benefits of this latter strategy for treating HSV cutaneous disease and recurrences. We also revisit and discuss antivirals and vaccine candidates against HSVs.
    Scopus© Citations 2  7
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    Norovirus: Facts and Reflections from Past, Present, and Future
    (2021)
    LUCERO, YALDA  
    ;
    David O. Matson
    ;
    Shai Ashkenazi
    ;
    Sergio George
    ;
    Miguel O’Ryan
    <jats:p>Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the “Norwalk virus” by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full biological and disease spectrum of Norovirus infection. Nevertheless, several areas remain incompletely understood due to the serious constraints to effectively replicate and propagate the virus. Here, we present a narrated historic perspective and summarize our current knowledge, including insights and reflections on current points of interest for a broad medical community, including clinical and molecular epidemiology, viral–host–microbiota interactions, antivirals, and vaccine prototypes. We also include a reflection on the present and future impacts of the COVID-19 pandemic on Norovirus infection and disease.</jats:p>
      1Scopus© Citations 56  3
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    NPC1 as a Modulator of Disease Severity and Viral Entry of SARSCoV- 2
    (2021)
    VIAL COX, MARIA CECILIA  
    ;
    CALDERON GIADROSIC, JUAN FRANCISCO  
    ;
    KLEIN POSTERNACK, ANDRES DAVID  
    <jats:sec> <jats:title /> <jats:p>The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.</jats:p> </jats:sec>
    Scopus© Citations 10  2
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    Successful treatment of cytomegalovirus retinitis with oral/intravitreal antivirals in HIV-negative patients with lymphoma
    (2022)
    Anastasia Tasiopoulou
    ;
    URZUA SALINAS, CRISTHIAN  
    ;
    Susan Lightman
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Objectives</jats:title> <jats:p>To report patients with systemic lymphoma and cytomegalovirus (CMV) retinitis, treated with a combination of oral and intravitreal antiviral agents on an outpatient basis.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Retrospective cases series. Information was gathered from the database of the Uveitis clinics at Moorfields Eye Hospital, United Kingdom from December 2014 to December 2018. The inclusion criteria comprised the diagnosis of systemic lymphoma, associated with a diagnosis of CMV retinitis. Exclusion criteria were alternative ocular diagnosis, human immunodeficiency virus (HIV), primary intraocular lymphoma, or other causes of immunosuppression.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>All seven subjects had been under oncologist care for systemic lymphoma. CMV retinitis presented with a median of 61 months after the systemic lymphoma diagnosis. Five patients underwent a vitreous biopsy, and four of them returned PCR positive for CMV and the fifth patient had PCR positive in a blood sample. All patients were treated with oral Valganciclovir, with an induction dose of 900 mg every 12 h for up to 3 weeks until disease resolution and a maintenance dose thereafter. All but one received additional intravitreal Foscarnet injections, with a dose of 2.4 mg /0.1 ml.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The management of patients with systemic lymphoma and CMV retinitis with oral and intravitreal antiviral agents, resulted in effective disease control.</jats:p> </jats:sec>
      1Scopus© Citations 6
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    Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants
    (2020)
    Eric A F Simões
    ;
    Eduardo Forleo-Neto
    ;
    Gregory P Geba
    ;
    Mohamed Kamal
    ;
    Feng Yang
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14–1.05 in the 1-dose group and .39 [95% CI, .14–1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73–2.56] in the 1-dose group and 1.69 [95% CI, .92–3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2–amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trials Registration</jats:title> <jats:p>NCT02325791.</jats:p> </jats:sec>
    Scopus© Citations 72  1
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      44  1Scopus© Citations 38
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    Direct‐Acting Antivirals and Hepatocellular Carcinoma: No Evidence of Higher Wait‐List Progression or Posttransplant Recurrence
    (2020)
    Federico Piñero
    ;
    Ilka Boin
    ;
    Aline Chagas
    ;
    Emilio Quiñonez
    ;
    Sebastián Marciano
      7Scopus© Citations 15