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Erick Acocal-Juárez,1– 3 Luis Márquez-Domínguez,2 Verónica Vallejo-Ruíz,2 Lilia Cedillo,3 Gerardo Santos-López2 1Centro de Investigaciones en Ciencias Microbiológicas, Benemérita Universidad Autónoma de Puebla, Puebla Pue, Mexico; 2Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico; 3Centro de Detección Biomolecular, Benemérita Universidad Autónoma de Puebla México, Puebla Pue, MexicoCorrespondence: Lilia Cedillo; Gerardo Santos-López, Email lilia.cedillo@correo.buap.mx; gerardo.santos.lopez@gmail.comAim: Influenza control demands multifaceted strategies, including antiviral drugs. Baloxavir, a recent addition to influenza treatment, acts as an inhibitor of the Polymerase acid (PA) component of the viral polymerase. However, mutations associated with resistance have been identified.Purpose: This study analyzed PA gene sequences of influenza A and B viruses (IAV and IBV, respectively) reported in the Americas, retrieved from databases published until May 2023, to identify primary markers of resistance to baloxavir.Patients and Methods: PA gene sequences were obtained from the GISAID and NCBI databases, focusing on countries in the Americas with 500 or more sequences for IAV, and 50 or more sequences for IBV.Results: Of the 58,816 PA sequences analyzed for IAV, only 55 (0.1%) harbored resistance markers, representing approximately 1 in 1000 occurrence. The most frequent markers were I38V (21 cases) and I38M (7 cases) at position 38 of PA, followed by E199G (9 cases) at position 199. For IBV, 14,684 sequences were analyzed, of which only eight presented a resistance marker (0.05%). Five sequences had the M34I marker, while the remaining three had the I38V marker. While frequency of resistance markers in PA is comparable to other regions, these results highlight the need for enhanced sequencing efforts, particularly in Latin America. Such efforts would serve to intensify influenza surveillance and inform public health interventions.Conclusion: While baloxavir demonstrates efficacy against influenza, resistance markers have been identified, including pre-existing ones. Our study adds eight (IAV: six and IBV: two) new spontaneously occurring substitutions to the existing literature, highlighting the need for continued surveillance. Among these, I38M stands out due to its significant tenfold reduction in drug susceptibility. Therefore, vigilant monitoring of these resistance markers in IAV and IBV remains crucial for maintaining baloxavir’s effectiveness and informing future public health interventions.Keywords: antiviral resistance, substitutions, PA protein, polymerase inhibitor

William Toledo-Rueda,1,2 Nora H Rosas-Murrieta,3 José E Muñoz-Medina,4 César R González-Bonilla,4 Julio Reyes-Leyva,1 Gerardo Santos-López1 1Laboratory of Molecular Biology and Virology, Eastern Biomedical Research Center, Mexican Institute of Social Security, Metepec, Puebla, Mexico; 2Postgraduate in Chemical Sciences, Autonomous University of Puebla, Puebla, Mexico; 3Laboratory of Biochemistry and Molecular Biology, Chemistry Center, Institute of Science, Autonomous University of Puebla, Puebla, Mexico; 4Division of Laboratories for Surveillance and Epidemiological Research, Coordination of Epidemiological Surveillance, Mexican Institute of Social Security, Mexico City, Mexico. Background: Influenza causes high rates of morbidity and mortality. Genetic variability of influenza viruses generates resistance to antivirals, which are of two types, since they act on two different viral targets: adamantanes, which block the M2 ion channel, and the neuraminidase (NA) inhibitors. Methods: In Mexico, the available studies on the antiviral resistance of circulating influenza strains are scarce, so this work undertook an analysis of the Mexican sequences reported in public gene banks to perform a systematic analysis of the antiviral resistance markers on both M2 and NA. In all, 284 M2 sequences and 423 NA sequences were retrieved from three genetic databases (sequences from 2000 to 2017 were considered). Results: The resistance markers to M2 blockers were present in 100% of H1N1 pdm2009, 83.6% of H3N2, and 5.8% of seasonal H1N1 sequences. Two resistance markers conferring resistance to NA inhibitors were present in seasonal H1N1 sequences, H275Y (50.0%) and N70S (33.3%). None of these viruses had both resistance markers, which are associated with oseltamivir resistance. The more frequent resistance marker in H1N1 pdm2009 NA sequences was H275Y, present in 3.6%, while S247N was present in 0.30%. Only one of the resistance-associated markers (Q136K) in NA (1.5%) was present in the analyzed H3N2 sequences, while sequences of influenza B virus did not present resistance markers to NA inhibitors. Some influenza A H1N1 pdm2009 sequences (1.8%) presented resistance markers to both M2 and NA. Conclusion: Based on the present analysis, 7.1% of the all serotypes of influenza virus A sequences analyzed in Mexico from 2000 to 2017 have mutations conferring resistance to NA inhibitors. Because of this, and the limited availability of influenza drugs, it is necessary to increase the epidemiological surveillance, including molecular analysis, which will provide data such as the presence of changes associated with antiviral resistance. Keywords: influenza A virus, drug resistance, M2 blockers, neuraminidase inhibitors, oseltamivir, zanamivir

Carolina Jasso-Miranda,1,2 Irma Herrera-Camacho,2 Lilian Karem Flores-Mendoza,3 Fabiola Dominguez,1 Veronica Vallejo-Ruiz,1 Gilma Guadalupe Sanchez-Burgos,4 Victoria Pando-Robles,5 Gerardo Santos-Lopez,1 Julio Reyes-Leyva11Laboratory of Immunology and Virology, East Biomedical Research Center, Mexican Institute of Social Security (IMSS), CP 74360 Metepec, Puebla, México; 2Laboratory of Biochemistry and Molecular Biology, Center of Chemistry, Institute of Sciences, Meritorious Autonomous University of Puebla, CP 72570 San Manuel, Puebla, Mexico; 3Department of Chemical, Biologic and Agricultural Sciences, Science and Enginery Division, University of Sonora, CP 85880 Navojoa, Sonora, Mexico; 4Yucatan’s Medical Research Unit, Mexican Institute of Social Security (IMSS), CP 97150 Merida, Yucatan, Mexico; 5Infectious Disease Research Center, National Institute of Public Health, CP 62100 Cuernavaca, Morelos, MexicoBackground: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue.Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection.Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely.Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on anti-inflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p

Competing Interests: The authors report no conflicts of interest in this communication.

Purpose: Cervical cancer (CC) is the second most frequent cancer in undeveloped countries. Serum biomarkers could be useful for evaluation of the treatment response and as a complementary means to improve diagnosis. The expression of galectin-9 is altered in cancer tissue, and higher concentrations are found in the serum of cancer patients. The objectives of this study were (a) to determine the serum galectin-9 concentration in patients with intraepithelial lesions and CC, (b) to determine if the concentration was related to the clinicopathological characteristics and (c) to determine if the galectin-9 concentration was related to its expression level in tumour tissue., Patients and Methods: In all, 222 serum samples from women with different diagnoses, including premalignant lesions and CC, as well as samples from women with normal cytology were included in the study. The serum galectin-9 concentration was determined by ELISA. To evaluate the expression level of galectin-9 in CC tissue, immunohistochemistry was performed in 34 CC biopsy specimens., Results: The galectin-9 concentration in the serum of CC patients (8.171 ng/mL) was increased compared with serum from women with normal epithelia (4.654 ng/mL) and those with low-grade (4.806 ng/mL) and high-grade (5.354 ng/mL) intraepithelial lesions (p value < 0.0001). The area under the ROC curve considering the CC group and the control group was 0.882. The optimal cut-off value was ≥6.88 ng/mL, the specificity obtained was 100%, and the sensitivity was 68.2%. In the CC group, the analysis of the clinical stage showed an increase of galectin-9 in the advanced stage IV group. Serum galectin-9 was not related to the level of galectin-9 expression in tissue, which suggests that galectin-9 is not secreted by tumour cells., Conclusion: The serum galectin-9 concentration is related to cancer progression, as the level of this protein is higher in patients with advanced-stage disease., Competing Interests: Dr Julio Reyes-Leyva reports grants from Consejo Nacional de Ciencia y Tecnología, during the conduct of the study. The authors report no conflicts of interest related to this work., (© 2022 Reyes-Vallejo et al.)