In vitro Antiviral Activity of Eucheuma cottonii against New Castle Disease Virus

Aims: To determine the antiviral activity of Eucheuma cottonii against the New Castle disease virus. Study Design: In vitro study. Place and Duration of the Study: The research was conducted in the Pharmaceutical Chemistry, Drug Design, and Pharmacognosy department at St. John’s University of Tanzania and Virology Laboratory at Sokoine University of Agriculture between April 2022 and August 2022. Methodology: The present study used an OVO assay and hemagglutination test to investigate the In vitro antiviral activity of E. cottonii collected from Zanzibar, Tanzania, against the Newcastle disease virus (NDV). Ovo assay was assessed using 60 embryonated eggs and a hemagglutination test was performed by collecting the allantoic fluid from treated eggs and serum from hatched chicks to detect antigen titer against NDV using 96 well plate diffusion method. Results: Results of the Ovo assay showed that all the 40 embryonated eggs used as test group were alive and thus confirmed that the extract of E. cottonii (0.32 g/mL) is strong enough to destroy the virus. In which the results from the serial dilution assay (hemagglutination test) confirmed a substantial decrease in the high level of NDV as observed in the allantoic fluid of the infected embryonated eggs to range from 10

Evaluation of Withania somnifera based supplement for immunomodulatory and antiviral properties against viral infection

Background: Viral mediated diseases are continuously posing potent threat to human health. Nutraceuticals are being employed as novel therapeutics during viral outbreaks. MAM granules consist of Curcuma longa, Withania somnifera, and Piper nigrum, is one such patented Siddha nutraceutical supplement that has been proposed to be a therapeutic agent against viral diseases. Objective: We characterised MAM for their phytochemical and physicochemical properties and evaluated its cytotoxicity via in vivo acute toxicity studies using Wistar rats and by cell-based MTT assays. Materials and Methods: The antiviral properties of the aqueous extract of MAM were investigated against SARS- CoV-2 and chikungunya virus (CHIKV). Further, using ABTS radical scavenging, SOD enzymatic assays and measurement of intracellular ROS, we investigated the antioxidant potential of MAM extract and its ingredients in RAW264.7 cells. Additionally, production of inflammatory mediators was evaluated via NO release, PGE2 production and release of pro-inflammatory cytokines (IL-1? and TNF?). Results: The MAM granules and aqueous extracts demonstrated no significant toxicity and demonstrated potent antiviral activity during co-incubation assay with SARS-CoV-2 and CHIKV. Moreover, we observed potent antioxidant and anti-inflammatory activity of MAM extract in a dose dependent manner. Further investigations on the individual ingredients with respect to their antioxidant and anti-inflammatory activities showed that all ingredients contributed synergistically and Withania somnifera showed most potent anti-oxidant activity. Conclusion: The overall in vitro, and in vivo analysis demonstrated that MAM granules were non-toxic and possessed potent antiviral activity. Additionally, observed significant anti-oxidant and anti-inflammatory prop- erties of MAM suggested the modulation of innate immune response in the host validating its use as an effective nutraceutical during viral outbreaks.

Transmisión intradomiciliaria de la viruela del simio / Household transmission of monkeypox

RESUMEN La viruela del simio es una enfermedad poco frecuente causada por el virus de la viruela del simio (MPXV). Este es un virus que puede ingresar al huésped a través de diferentes vías, como la orofaringe, la nasofaringe, rutas intradérmicas, entre otras. En el año 2022 se supo de un brote en el que el virus parecía tener mutaciones que le harían propagarse de manera más eficiente. Presentamos tres casos de viruela del simio en el seno de una familia de ocho miembros. El paciente 1, un hombre de 32 años, presentó una pápula debajo del ojo izquierdo, la cual fue eclosionada manualmente por su esposa; luego presentó endoftalmitis asociada a fiebre y cefalea, añadiéndose lesiones pruriginosas tipo vesiculares no dolorosas en extremidades y genitales. Finalmente, se le diagnosticó, clínicamente, infección por viruela del simio. La paciente 2, una mujer de 27 años (pareja del paciente 1), presentó lesiones vesiculares y pustulares en el tórax, las extremidades y la región anal seis días después de exposición por contacto estrecho con el paciente 1. Luego, se le adicionaron mialgias, fiebre y odinofagia, con resultado positivo a prueba molecular para MPXV. El paciente 3, un niño de ocho años, a los siete días del inicio de síntomas de la madre (paciente 2), presentó odinofagia, tinnitus, fiebre, adenopatía cervical y pápulas umbilicadas en el abdomen, el brazo izquierdo y el glúteo derecho, con resultado positivo a prueba molecular para MPXV. Los otros miembros de la familia no presentaron manifestaciones clínicas a pesar del contacto intrafamiliar prolongado de aproximadamente dos semanas con los pacientes, en el que compartieron áreas comunes y utensilios sin restricciones.

ABSTRACT Monkeypox is a rare disease caused by the monkeypox virus (MPXV). This virus can enter the host through different routes, such as the oropharynx, nasopharynx and intradermal routes, among others. In 2022, an outbreak was reported in which the virus seemed to have mutations that would make it spread more efficiently. We present three cases of monkeypox in a family of eight members. Patient 1, a 32-year-old man, presented with a papule under the left eye, which was hatched manually by his wife. He then developed endophthalmitis associated with fever and headache, in addition to nonpainful vesicular pruritic lesions on the extremities and genitalia. He was eventually clinically diagnosed with monkeypox infection. Patient 2, a 27-year-old woman (wife of patient 1), presented with vesicular and pustular lesions on the chest, extremities and anal area six days after exposure through close contact with patient 1. She subsequently developed myalgia, fever and odynophagia, with a positive molecular test result for MPXV. Patient 3, an 8-year-old boy, presented with odynophagia, tinnitus, fever, cervical lymphadenopathy, and umbilicated papules on the abdomen, left arm, and right buttock seven days after the onset of symptoms in his mother (patient 2). He also tested positive for MPXV on a molecular test. The other family members did not present clinical manifestations despite being in intrafamilial contact with the patients for approximately two weeks, during which they shared common areas and utensils without restrictions.

Successful management of hepatitis B and C coinfection: a case report / Manejo exitoso de un caso de coinfección por hepatitis B y C: reporte de caso

ABSTRACT We report the case of a patient with chronic hepatitis B and C managed with direct-acting antivirals in an outpatient setting. Chronic hepatitis B was first treated with entecavir before initiating treatment for chronic hepatitis C. The patient achieved viral suppression for hepatitis B and sustained virological response for hepatitis C. As direct-acting antivirals become more available, healthcare practitioners should be familiar with managing patients with chronic coinfection.

RESUMEN Reportamos el caso de un paciente con infección crónica por hepatitis B y C, tratado con antivirales de acción directa de manera ambulatoria. Primero se trató la infección crónica por hepatitis B con entecavir, antes de iniciar el tratamiento para la infección crónica por de salud debe estar familiarizado con el manejo de pacientes con coinfección crónica.

Computer-aided drug design of novel nirmatrelvir analogs inhibiting main protease of Coronavirus SARS-CoV-2

A computer-aided drug design of new derivatives of nirmatrelvir, an orally active inhibitor of the main-protease (Mpro) of the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), was performed to identify its analogs with a higher antiviral potency. The following workflow was used: first, an evolutionary library composed of 1,866 analogs was generated starting from a parent nirmatrelvir scaffold and going through small mutation, fitness scoring, ranking, and selection. Second, the generated library was preprocessed and filtered against a 3-D pharmacophore model of nirmatrelvir built from its X-ray structure in a co-crystalized complex with the Mpro enzyme, allowing us to reduce the chemical space to 32 active analogs. Third, structure-based molecular docking against two different enzyme structures further ranked these active candidates, so that up to eight better-binding analogs were identified. The selected hit-analogs target the Mpro enzymes of SARS-CoV-2 with a higher binding affinity than a parent nirmatrelvir. The main structural modifications that increase the overall inhibitory affinity are identified at the azabicyclo[3.1.0] hexane and 2-oxopyrrolidine fragments. A characteristic structural feature of the inhibitor binding with the Mpro active center is the similar location of the trifluoroacetylamino fragment, which is observed for most hit-analogs. The suggested workflow of the computer-aided rational design of new antiviral noncovalent inhibitors based on the scaffold of approved drugs is a promising, extremely low-cost, and time-efficient approach for the development of new potential pharmaceutical ingredients for the treatment of Coronavirus Disease 2019.

Do oral antiseptics used in the dental routine have anti-viral efficacy? a systematic review of in vitro studies / Os antissépticos orais utilizados na rotina odontológica têm eficácia anti-viral? Uma revisão sistemática de estudos in vitro / ¿Los antisépticos orales utilizados en la rutina odontológica tienen eficacia antiviral? Una revisión sistemática de estudios in vitro

Introduction: Mouthwashes play an important role in the dental clinic, but their role on viruses requires investigation. Objective:to review in vitro studies to identify the effect of different mouthwashes on the main viruses associated with routine dental care. Methodology:The following databases were searched in September 2023: PubMed, Embase, Scopus and Web of Science databases; the Cochrane Library and the Virtual Health Library (VHL); and grey literature. In vitro studies that used mouthwashes to reduce the viral load were selected. The PICOS strategy was considered to define eligibility criteria: the Population (viruses involved in the etiology of oral infection), the Intervention (oral antiseptics), the appropriate comparator (positive and negative controls), the Outcomes of interest (reduction of viral load) and the Study design (in vitro studies). Results:Considering the eligibility criteria, 19 articles were included in this review. The efficacy of povidone-iodine (PVP-I), chlorhexidine, Listerine®, essential oils, and cetylpyridinium chloride (CPC) rinses were investigated. PVP-I (0.23%) had its effects mainly associated with coronaviruses SARS(Severe Acute Respiratory Syndrome),demonstrating a significant reduction in viral load after 15 seconds of exposure. Chlorhexidine (0.05%; 0.1% and 0.5%) was ineffective against adenovirus, poliovirus, and rhinovirus respiratory viruses. Listerine® demonstrated superior efficacy against HSV-1 and 2 viruses and influenza A, and cetylpyridine chloride also demonstrated virucidal activity against influenza A. Conclusions:The type, concentration, and time of exposure to antiseptics varied between studies. PVP-I and chlorhexidine digluconate were the most studied substances, butin general, PVP-I was more effective in reducing viral titers, especially concerning coronaviruses. Other antiseptics such as CPC, H2O2 and Listerine® have also shown significant reduction in viral load, but this is a limited number of studies (AU).

Introdução: Os enxaguantes bucais desempenham um papel importante na clínica odontológico, porém seu papel sobre os vírus requer investigações. Objetivo: revisar estudos in vitro para identificar o efeito de diferentes colutórios sobre os principais vírus associados ao atendimento odontológico de rotina. Metodologia: As seguintes bases foram pesquisadas até setembro de 2023: PubMed, Embase, Scopus e Web of Science; a Biblioteca Cochrane e a Biblioteca Virtual em Saúde (BVS); e literatura cinzenta. Foram selecionados estudos in vitro que utilizaram bochechos com o objetivo de reduzir a carga viral. A estratégia PICOS foi considerada para a definição dos critérios de elegibilidade: População (vírus envolvidos na etiologia da infecção oral), Intervenção (antissépticos orais), Comparador (controles positivos e negativos), os Desfechos de interesse (redução da carga viral) e o desenho do estudo (estudos in vitro). Resultados: Considerando os critérios de elegibilidade, 19 artigos foram incluídos para esta revisão. A eficácia da povidona-iodo (PVP-I), clorexidina, Listerine®, óleos essenciais e lavagens com cloreto de cetilpiridínio foram investigadas. O PVP-I(0.23%)teve seus efeitos principalmente associados ao coronavírusSARS (Síndrome Respiratória Aguda Severa),demonstrando uma redução significativa da carga viral após 15 segundos de exposição. A clorexidina mostrou-se ineficaz contra vírus respiratórios de adenovírus, poliovírus e rinovírus. Listerine® demonstrou eficácia superior contra vírus HSV-1 e 2 e vírus influenza A, e cloreto de cetilpiridinio também demonstrou atividade virucida contra influenza A.Conclusões:O tipo, concentração e tempo de exposição aos antissépticos variaram entre os estudos. O PVP-I e o digluconato de clorexidina foram as substâncias mais estudadas, mas no geral, o PVP-I foi mais eficaz na redução dos títulos virais, principalmente no que diz respeito aos coronavírus. Outros antissépticos como CPC, H2O2 e Listerine® também mostraram redução significativa da carga viral, mas trata-se de um número limitado de estudos (AU).

Introducción: Los enjuagues bucales son importantesen la clínica dental, sin embargo, su efecto sobre los virus requiere investigaciones. Objetivo: Revisar estudios in vitro para identificar el efecto de enjuagues bucales sobre los principales virus asociados con larutinaodontológica. Metodología: Las siguientes bases de datos fueron investigadas hasta septiembrede 2023: PubMed, Embase, Scopus y Web of Science; Biblioteca Cochrane y Biblioteca Virtual en Salud (BVS); yliteratura gris. Se seleccionaron estudios in vitro que utilizaron enjuagues bucales con el objetivo de reducir la carga viral. Se consideró la estrategia PICOS para definir los criterios de elegibilidad: Población (virus implicados en la etiología de la infección oral), Intervención (antisépticos bucales), Comparador (controles positivos y negativos), Resultados de interés (reducción de la carga viral) y diseño del estudio (in vitro). Resultados: Considerando los criterios de elegibilidad, se incluyeron 19 artículos.Se investigó la eficacia de povidona yodada (PVP-I), clorhexidina, Listerine®,aceites esenciales y enjuagues de cloruro de cetilpiridinio (CPC). PVP-I(0.23%)mostró sus efectos principalmente asociados al coronavirus SARS(Síndrome Respiratorio Agudo Severo), demostrando una reducción significativa de la carga viral después de 15 segundos. Se ha demostrado que la clorhexidina es ineficaz contra losvirus respiratorios adenovirus, poliovirus y rinovirus. Listerine® demostró una eficacia superior contra los virus HSV-1 y 2 y el virus de la influenza A, y el CPCtambién mostró actividad virucida contra la influenza A.Conclusiones: El tipo, la concentración y el tiempo de exposiciónvariaron entre los estudios. PVP-I y digluconato de clorhexidina fueron las sustancias más estudiadas, pero,PVP-I fue más efectiva en la reducción de los títulos virales, especialmente en lo que respecta a los coronavirus. Otros antisépticos como CPC, H2O2 y Listerine® también mostraron una reducción significativa de la carga viral, pero se trata de un número limitado de estudios (AU).

Relación entre el virus herpes simple y la periodontitis estadio IV: Una revisión sistemática de literatura / Relationship of herpes simplex virus and stage IV periodontitis: A systematic review of the literature

RESUMEN Objetivo: Este trabajo tiene como propósito determinar, mediante una revisión sistemática de literatura, la relación entre el virus del herpes simple (VHS) y la periodontitis estadio IV, con el fin de orientar la terapéutica para el tratamiento de esta entidad. Metodología: Revisión sistemática de literatura en las bases de datos PubMed, Elsevier, Science Direct y SciELO, empleando la lista de comprobación PRISMA. Se incluyeron revisiones sistemáticas y metaanálisis sobre diseños de estudios experimentales, estudios de biología molecular y estudios in vivo humanos acerca de la relación del herpes virus simple tipo 1 y la periodontitis estadio IV, publicados entre el 2017 y 2022, en español e inglés, en una búsqueda que se realizó entre el 8 y 22 de abril de 2022. Tres artículos resultaron elegibles, aplicando los criterios de inclusión y exclusión, de un total inicial de 1.797. Resultados: Las revisiones examinadas comprueban una relación más convincente del virus del herpes humano, aumentada por su presencia y asociación con la enfermedad periodontal en estadios avanzados, como la periodontitis estadio IV, en comparación con pacientes sanos y con gingivitis. Conclusiones: El manejo farmacológico coadyuvante de la terapia periodontal en pacientes con periodontitis estadio IV, acompañado de terapia antibiótica y antiviral, puede reducir o erradicar el herpes simple en sitios con enfermedad periodontal.

ABSTRACT Objective: The purpose of this study is to determine, through a systematic review of the literature, the relationship between the herpes simplex virus (HSV) and stage IV periodontitis to guide therapeutics for the treatment of this entity. Methodology: The method was a systematic review of the literature in PubMed, Elsevier, Science Direct and SciELO databases, using the PRISMA checklist. Systematic review documentation and meta-analysis about experimental study designs, molecular biology studies, and in vivo studies on the relationship between herpes simplex virus type 1 and stage IV periodontitis, published between 2017 and 2022, in Spanish and English were obtained in a search conducted between April 8 and 22, 2022. Three articles were eligible after applying the inclusion and exclusion criteria, out of an initial total of 1.797. Results: The reviewed articles show a more consistent relationship of the human herpes virus, increased by its presence and association with advanced stage periodontal disease, such as stage IV periodontitis, compared to healthy patients and patients with gingivitis. Conclusion: Pharmacological management as adjuvant of periodontal therapy in patients with stage IV periodontitis, accompanied by antibiotic and antiviral therapy, can reduce or eliminate herpes simplex in sites with periodontal disease.

COVID-19 pandemic period - adverse drug reactions reporting, observing, assessing and analyzing at tertiary care teaching hospital, IMS-BHU Varanasi – 3-years observational study

Background: Effects of drugs that are undesirable and beyond their therapeutic effect are labeled as adverse drug reactions (ADRs). These often lead to increase hospital stay, repeated hospitalization, adversely affecting the quality of life, and perhaps, one of the causes of mortality making it a chief challenge in modern health-care system. This observational study analyzed and summarized details linked to ADRs identification, reporting, severity, treatment, and preventive measures for health professionals. Aims and Objectives: The objectives of the study are to assess and evaluate demographic profile, drug prescribed with its dosage, clinical findings, seriousness, outcome, causality, and organ system affected by concerned ADRs. Materials and Methods: An observational prospective study analyzing submitted ADRs mentioned in individual case safety reports (ICSR), mentioning demographics profile, suspected drug, involved bodily organ system, causality and reaction severity in different age groups of indoor and outdoor patients reported from 2020 January to 2022 December at ADR monitoring center, Department of Pharmacology, IMS-BHU. Performa used for ADRs reporting is ICSR, which later on transferred to the Indian database (VigiFlow) for data collection and analysis. Results: Total 1096 ADRs were identified and reported in 36-month duration, with male (629/1096) to female (466/1096) ratio of 1.35:1. On age group analysis, 74.8% (820/1096) adults (18–59 years) followed by 23.4% (256/1096) elderly (>59 years) and only 1.8% (20/1096) children and adolescents (<17 years) cases were found. Endocrine system was the most common organ system affected with 27.9% case (306/1096), succeeded by 25.4% (278/1096). ADRs were linked to the gastrointestinal system and 15.69% (172/1096) cases were related to dermatological problems. Drugs belonging to antimicrobial drug group were the most involved comprising of 668/1096(60.94%) cases which includes mainly antibiotics, anti-viral and anti- fungal drugs. On further analyzing and classifying, it was found that majority of ADRs were due to anti-viral drugs, followed by antibiotics with 31.02% (340/1096) cases and 27.09% (297/1096) cases, respectively. Antiallergic and antifungal drug groups were found be least involved with only 1.6% (17/1096) cases each. On assessment of causality, majority of ADRs were possible in 60.40% (662/1096) cases and probable in 39.14% (429/1096) cases. Conclusion: Occurrence of ADRs is very common and perhaps a serious concern regarding well-being and safety of public as may lead to non-serious to serious health problems. This observational study identified the need of increased awareness of ADR monitoring, reporting and benefits, to fulfill the space created by under- reporting, especially in geriatrics and pediatric age group patients. A detail evaluation and removal of the obstacles faced by these agegroups during process of reporting ADRs is important so that all the patients may easily approach for spontaneous reporting of side effects after start usage of any medicinal product, if any. In addition, surveillance studies emphasizing on reporting are essential for early recognition, detection, and avoidance of ADRs leading to appropriate with safe usage of drugs.

Drugs and natural products for the treatment of COVID-19 during 2020, the first year of the pandemic / Fármacos y productos naturales para el tratamiento de la COVID-19 durante 2020, el primer año de la pandemia

Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

In Silico Study of Organic Compounds from Dipteryx odorata with SARS-COV-2 Targets by Molecular Docking and ADME-TOX Analysis

Introduction: The new coronavirus SARS-CoV-2, identified in December 2019 as the cause of COVID-19, has triggered an outbreak of potentially fatal atypical pneumonia. The constant search for new molecules or strategies to combat this disease continues. Thus, the objective of this work was to evaluate, using in silico methods, the compounds present in Dipteryx odorata as inhibitors of crucial targets of SARS-COV-2. Methodology: The methodology included the selection of plant compounds from the Pubchem database and obtaining the structures of SARS-COV-2 proteins (6vxx, 6lu7, 1R42) from the Protein Data Bank (PDB). The molecular docking analysis was performed using the Autodock Tools 1.5.6 and Autodock Vina programs, LigPlus to obtain amino acids, and Chimera v.13.1 to generate 3D images. The absorption, distribution, metabolism, excretion and toxicity (ADME-TOX) properties of the most promising compounds were evaluated with the pkCSM tool. Results: In total, 672 molecular dockings were carried out, tested with 168 ligands, resulting in 17 compounds with binding energies lower than -7.9 kcal.mol-¹. A highlight was the exceptional interaction of the vouacapenic acid compound with the Spike protein, recording an energy of -9.9 kcal.mol-¹. The study revealed that compounds such as vouacapenic acid, taraxasterol and luteolin showed notable interactions with the Spike protein, in addition to positive results in the ADMET-TOX profile. Conclusion: These findings indicate the potential of these compounds and point to the need for in vivo and in vitro studies to validate their antiviral efficacy as therapeutic agents against SARS-COV-2.

The infusion of Baccharis spicata (Lam. ) Baill (Asteraceae) has antiviral activity against hepatitis B virus without cytotoxic effects against several cell lines / La infusión de Baccharis spicata (Lam. ) Baill (Asteraceae) posee actividad antiviral contra el virus de la hepatitis B sin efectos citotóxicos contra varias líneas celulares

Medicinal plants are used to cure diseases, and their replacement is frequent and affects public health. The genus Baccharis has representatives within the medicinal flora of Argentina, although the replacement of the species of this genus known under the vulgar name of "carqueja" by Baccharis spicata has been detected i n herbalists or markets of herbal products. The genotoxic safety of this species has been established in previous work of our group. The aim of this study was to evaluate the antiviral activity of an infusion made from B. spicata leaves against hepatitis B virus with the HepG2.2.15 cellular system and to determine cytotoxicity in HepG2.2,15, A549 and Vero cell lines. Infusion of B. spicata was active to inhibit HBV replication with an EC 50 of 22.54 µg/mL and a CC 50 of 190 µg/mL.

Las plantas medicinales son empleadas para la cura de enfermedades, y su sustituc ión es frecuente y afecta a la salud pública. El género Baccharis posee representantes dentro de la flora medicinal de Argentina, aunque se ha detectado la sustitución de las especies de dicho género conocidas bajo el nombre vulgar de "carqueja" por Baccha ris spicata en herboristerías o mercados de productos herb arios . Se ha establecido la seguridad genotóxica de esta especie en trabajos previos de nuestro grupo. Este estudio buscó evaluar la actividad antiviral de una infusión elaborada a partir de hojas de B. spicata frente al virus de la hepatitis B con el sistema celular HepG2.2.15 y determinar la citotoxicidad en las líneas celulares HepG2.2.15, A549 y Vero. La infusión de B. spicata fue activa para inhibir la replicación del virus con un EC 50 de 22.54 µg/mL y un CC 50 de 190 µg/mL.

Experimental study on pharmacodynamics of Su Bei Zhi Ke granules (SBZKG) for acute tracheobronchitis / 中国临床药理学与治疗学

AIM: To observe the effect of Su Bei Zhi Ke granules (SBZKG) on acute tracheobronchitis (Syndrome of Wind-cold Attacking Lung). METHODS: Mouse ear swelling experiment and mouse abdominal capillary permeability experiment was used to observe its anti-inflammatory effect. Cough test in mice induced by ammonia water, and phlegm test in rats were used to observe the expectorant and antitussive effects of phenol red test in mice. We used the mortality rate experiment of infected mice to observe its antibacterial and antiviral effects. RESULTS: Compared with the contral group, the large and medium dose groups of SBZKG both reduced mouse auricle swelling (P<0.05) and increased swelling inhibition rate, reducing mouse abdominal capillary permeability (P<0.05, P<0.01). SBZKG can increase the phenol red sputum output in the respiratory tract of mice (P<0.01), prolong the cough incubation period of mice, reduce the number of coughs in mice (P<0.05, P<0.01), and increase the sputum output in rats (P<0.05, P<0.01). SBZKG can reduce the mortality rate of mice infected with bacteria and viruses. CONCLUSION: SBZKG has certain anti-inflammatory, antitussive, expectorant, antibacterial and antiviral effects, and has certain therapeutic effects on acute tracheobronchitis.

Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection / 中国实验方剂学杂志

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Hepatitis C virus infection and organ transplantation / 临床肝胆病杂志

In recent years， rapid progress has been made in strategies for the prevention and treatment of hepatitis C virus （HCV） in organ transplant candidates and recipients， and although HCV infections no longer threaten transplantation outcomes in liver or non-hepatic solid organ transplantation， they remain a focus of research. Since hepatitis C is still a leading cause of death worldwide due to decompensated cirrhosis， liver failure， and hepatocellular carcinoma， appropriate organ transplantation is needed to improve survival rate and quality of life. With the increase in HCV-positive solid organ donors in recent years and the fact that the demand for organs still greatly exceeds organ supply， as well as the development of direct-acting antiviral agents， transplantation of HCV-viraemic organs into HCV-naïve recipients will significantly increase transplantation rates and reduce waitlist mortality. The efficacy of current HCV therapies has created an important opportunity to improve the survival rate of patients with end-organ failure by enhancing access to organ transplantation and reducing waitlist mortality.

Anti-SARS-CoV-2 activity of small molecule inhibitors of cathepsin L / 药学学报

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC50) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Effect of treatment with direct-acting antiviral agents on the prognosis of extrahepatic diseases in patients with hepatitis C / 临床肝胆病杂志

The prognosis of patients with hepatitis C virus infection depends not only on liver lesions， but also on extrahepatic sequelae. Direct-acting antiviral agents （DAAs）， as the first-line drugs in the treatment of hepatitis C， have helped more and more patients achieve sustained virologic response and clinical cure， but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure.

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Application status and prospect of organ from hepatitis C donor in solid organ transplantation / 器官移植

As a marginal organ donor, organs from hepatitis C donors have been applied in solid organ transplantation. While effectively alleviating the shortage of organs, it also faces certain challenges, such as the spread of hepatitis C virus (HCV). With the emergence and application of direct-acting antiviral agent, the cure of hepatitis C has gradually become a reality, laying the foundation for hepatitis C patients to become organ transplant donors. At present, with adjuvant treatment using antiviral drugs, certain efficacy has been achieved in solid organ transplantation from hepatitis C donors. In this article, research progress in kidney, heart, lung and liver transplantation from hepatitis C donors, the application of hepatitis C donors in solid organ transplantation and the safety and effectiveness of antiviral drugs were reviewed, and the feasibility of hepatitis C donors in solid organ transplantation was evaluated, aiming to provide reference for expanding the donor pool of organ transplantation and shortening the waiting time for organ transplantation in patients with end-stage diseases.

Analysis of Depression and Influencing Factors in HIV/AIDS Patients Receiving Antiviral Therapy / 中山大学学报(医学科学版)

ObjectiveTo investigate the depression status and its influencing factors in HIV/AIDS patients receiving antiviral therapy. MethodsFrom July 2022 to September 2022， successive sampling method was used to recruit HIV/AIDS patients receiving antiviral therapy from antiviral treatment institutions in Nanjing， and they were instructed to fill out anonymous questionnaires. The questionnaire collected the basic information of patients， and depression， HIV stigma score and social support level were investigated by Patient Health Questionnaire-9 （PHQ-9）， Berger HIV stigma scale （BHSS） and Multidimensional Scale of Perceived Social Support （MSPSS）. Multivariate Logistic regression was used to analyze the influencing factors of depression. ResultsA total of 1879 valid questionnaires were collected in this study， and the detection rate of depression was 50.1%. The results of multivariate logistic analysis showed that compared with patients with middle school or below， the risk of depression was lower for those with postgraduate or above ［OR=0.534， 95%CI （0.341， 0.835）， P=0.006］. Compared with antiviral therapy duration<1 year， antiviral therapy duration for 1 to 5 years ［OR=0.729， 95%CI （0.536， 0.991）］， >5 to 10 years ［OR=0.516， 95%CI （0.379， 0.702）］， >10 years ［OR=0.603， 95%CI （0.375， 0.969）］ was associated with a lower risk of depression. High level of social support was a protective factor for depression in HIV/AIDS patients compared with middle and low level of social support ［OR=0.430， 95% CI（0.349， 0.530）， P < 0.001］. There was a higher risk of depression with side effects than without side effects ［OR=2.260， 95%CI （1.833， 2.786）， P < 0.001］. The higher the score on the HIV stigma scale， the higher the possibility of depression was. ConclusionThe detection rate of depression of patients receiving antiviral therapy in Nanjing is high. After starting antiviral therapy， we should strengthen the monitoring of side effects and psychological status of patients， carry out psychological intervention， alleviate psychological problems， and improve the quality of life of patients receiving antiviral therapy.