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1.
Braz. j. biol ; 84: e253508, 2024. tab, ilus
Article in English | LILACS-Express | LILACS, VETINDEX | ID: biblio-1360218

ABSTRACT

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).


O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

2.
Rev. bras. ter. intensiva ; 34(1): 44-55, jan.-mar. 2022. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1388049

ABSTRACT

RESUMO Os medicamentos reaproveitados são importantes em contextos de recursos limitados porque as intervenções estão mais rapidamente disponíveis, já foram testadas com segurança em outras populações e são, em geral, mais baratas. Os medicamentos reaproveitados são uma solução eficaz, especialmente para doenças emergentes, como a COVID-19. O estudo REVOLUTIOn visa avaliar três medicamentos antivirais reaproveitados: atazanavir, daclatasvir e sofosbuvir, já utilizados em pacientes infectados pelo HIV ou pelo vírus da hepatite C, em um estudo randomizado, controlado por placebo, adaptativo, multibraço e em múltiplos estágios. Os medicamentos serão testados simultaneamente em um ensaio de Fase II para primeiro identificar se algum deles, isoladamente ou em combinação, reduz a carga viral. Se reduzirem, será iniciado um estudo de Fase III para investigar se tais medicamentos são capazes de aumentar o número de dias sem suporte respiratório. Os participantes devem ser adultos hospitalizados com idade ≥ 18 anos com início dos sintomas ≤ 9 dias e saturação de oxigênio ≤ 94% em ar ambiente ou necessidade de oxigênio suplementar para manter saturação de oxigênio > 94%. O tamanho total esperado da amostra varia entre 252 e 1.005 participantes, dependendo do número de estágios que serão concluídos no estudo. Assim, o protocolo é aqui descrito em detalhes, juntamente do plano de análise estatística. Em conclusão, o estudo REVOLUTIOn foi concebido para fornecer evidências se o atazanavir, o daclatasvir ou o sofosbuvir reduzem a carga viral de SARS-CoV-2 em pacientes com COVID-19 e aumentam o número de dias em que os pacientes ficam sem suporte respiratório. Neste artigo de protocolo, descrevem-se a fundamentação, o desenho e a situação do ensaio. Identificador do ClinicalTrials.gov:NCT04468087


ABSTRACT Repurposed drugs are important in resource-limited settings because the interventions are more rapidly available, have already been tested safely in other populations and are inexpensive. Repurposed drugs are an effective solution, especially for emerging diseases such as COVID-19. The REVOLUTIOn trial has the objective of evaluating three repurposed antiviral drugs, atazanavir, daclatasvir and sofosbuvir, already used for HIV- and hepatitis C virus-infected patients in a randomized, placebo-controlled, adaptive, multiarm, multistage study. The drugs will be tested simultaneously in a Phase II trial to first identify whether any of these drugs alone or in combination reduce the viral load. If they do, a Phase III trial will be initiated to investigate if these medications are capable of increasing the number of days free respiratory support. Participants must be hospitalized adults aged ≥ 18 years with initiation of symptoms ≤ 9 days and SpO2 ≤ 94% in room air or a need for supplemental oxygen to maintain an SpO2 > 94%. The expected total sample size ranges from 252 to 1,005 participants, depending on the number of stages that will be completed in the study. Hence, the protocol is described here in detail together with the statistical analysis plan. In conclusion, the REVOLUTIOn trial is designed to provide evidence on whether atazanavir, daclatasvir or sofosbuvir decrease the SARS-CoV-2 load in patients with COVID-19 and increase the number of days patients are free of respiratory support. In this protocol paper, we describe the rationale, design, and status of the trial. ClinicalTrials.gov identifier:NCT04468087

3.
Vitae (Medellín) ; 29(1): 1-11, 2022-01-09. Ilustraciones
Article in English | LILACS, COLNAL | ID: biblio-1363751

ABSTRACT

Background: Coronavirus infectious disease 2019 (COVID-19) caused by the infection with the new coronavirus SARS-CoV-2 has affected the life and health of more than 222 million people. In the absence of any specific pharmacological treatment, the need to find new therapeutic alternatives is clear. Medicinal plants are widely used worldwide to treat different conditions, including COVID-19; however, in most cases, there are no specific studies to evaluate the efficacy of these treatments. Objective: This article evaluates the antiviral effect of six plant extracts used by indigenous and afro Colombian people against SARS-CoV-2 in vitro. Methods: The antiviral effect of six extracts prepared from plants used in Colombian traditional medicine was evaluated against SARS-CoV-2 through a pre-post treatment strategy on the Vero E6 cell line. Once cytotoxicity was established through an MTT assay, the antiviral effect of the extracts was calculated based on the reduction in the viral titer determined by plaque assay. Results:Gliricidia sepium inhibited SARS-CoV-2 in a 75.6%, 56.8%, 62.5% and 40.0% at 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectively, while Piper tuberculatumtreatment reduced viral titer in 33.3% at 6 mg/mL after 48h. Conclusion:G. sepium and P. tuberculatum extracts exhibit antiviral activity against SARS-CoV-2 in vitro


Introducción: La enfermedad infecciosa causada por el coronavirus 2019 (COVID-19) generada por la infección con el nuevo coronavirus SARS-CoV-2 ha afectado la vida y la salud de mas de 222 millones de personas. En ausencia de algún tratamiento farmacológico específico, la necesidad de encontrar nuevas alternativas terapéuticas es clara. Las plantas medicinales son utilizadas en todo el mundo para tratar diferentes condiciones, incluyendo el COVID-19; sin embargo, en la mayoría de los casos no existen estudios específicos que evalúen la eficacia de estos tratamientos. Objetivo: En este artículo, evaluamos el efecto antiviral de seis extractos de plantas usadas por pueblos indígenas y afrocolombianos contra el SARS-CoV-2 in vitro.Metodología: El efecto antiviral de seis extractos preparados a partir de plantas usadas en medicina tradicional colombiana fue evaluado contra SARS-CoV-2 por medio de una estrategia de pre-post tratamiento en células Vero E6. Una vez se estableció la citotoxicidad por un ensayo de MTT, el efecto antiviral de estos extractos fue calculado basado en la reducción del título viral determinado por ensayo de plaqueo. Resultados:G. sepium inhibió SARS-CoV-2 en un 75.6%, 56.8%, 62.5% y 40.0% a 10 mg/mL, 8 mg/mL, 6 mg/mL, and 2 mg/mL, respectivamente. Mientras el extracto de Piper tuberculatum redujo el título viral en un 33.3% a 6 mg/mL luego de 48h de tratamiento


Subject(s)
Humans , SARS-CoV-2 , Antiviral Agents , Ethnobotany
4.
J. bras. pneumol ; 48(1): e20210393, 2022. tab, graf
Article in English | LILACS | ID: biblio-1360541

ABSTRACT

ABSTRACT Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = −0.01 (95% CI, −0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, −0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.


RESUMO Objetivo: Estudos na literatura sobre o uso de remdesivir no tratamento de pacientes com COVID-19 têm apresentado resultados divergentes. O objetivo deste estudo foi responder a perguntas a respeito do uso de remdesivir no tratamento de pacientes hospitalizados com COVID-19 moderada a grave. Métodos: Trata-se de uma revisão sistemática e meta-análise de ensaios clínicos controlados randomizados (ECR) de fase 3 e estudos observacionais de coorte recuperados de diversos bancos de dados, comparando pacientes hospitalizados com COVID-19 moderada a grave recebendo remdesivir a controles. Resultados: Foram recuperados 207 estudos, dos quais 9 preencheram os critérios de elegibilidade e foram incluídos no estudo. A meta-análise somente dos ECR não mostrou diferenças estatisticamente significativas entre os grupos remdesivir e controle quanto à mortalidade ou ao uso de ventilação mecânica/oxigenação por membrana extracorpórea, e a qualidade das evidências foi moderada e baixa, respectivamente. O uso de remdesivir aumentou a taxa de recuperação em 6% (IC95%: 3-9; p = 0,004) e a taxa de melhora clínica em 7% (IC95%: 1-14; p = 0,02). Além disso, não foram observadas diferenças significativas entre os grupos remdesivir e controle quanto à mortalidade quando a meta-análise concentrou-se apenas nos estudos observacionais de coorte [diferença de risco = −0,01 (IC95%: −0,02 a 0,01); p = 0,32; qualidade das evidências: moderada], e o risco de eventos adversos foi de 4% (IC95%: −0,08 a 0,01; p = 0,09). Conclusões: O uso de remdesivir no tratamento de pacientes com COVID-19 moderada a grave não teve impacto significativo em desfechos clinicamente importantes.


Subject(s)
Humans , COVID-19/drug therapy , Antiviral Agents/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Treatment Outcome , Alanine/analogs & derivatives , Observational Studies as Topic , SARS-CoV-2
5.
Evid. actual. práct. ambul ; 25(2): e007014, 2022. ilus, tab
Article in Spanish | LILACS, BINACIS, UNISALUD | ID: biblio-1380221

ABSTRACT

El nuevo tratamiento simplificado con antivirales orales para pacientes con Hepatitis C puede ser abordado desde la atención primaria, lo que facilita el acceso de la población afectada por esta infección crónica. En este artículo se repasan los aspectos claves del diagnóstico, el esquema de tratamiento simplificado y los candidatos a recibirlo. (AU)


The new simplified treatment with oral antivirals for hepatitis C patients can be approached at the primary care level, facilitating access for the population affected by this chronic infection. This article reviews the key aspects of the diagnosis, the simplified treatment scheme, and the eligible candidates for the treatment. (AU)


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Antiviral Agents/administration & dosage , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Primary Health Care , Enzyme-Linked Immunosorbent Assay , Hepatitis C/blood , Persistent Infection/diagnosis , Persistent Infection/drug therapy , Persistent Infection/blood , Liver Cirrhosis/diagnosis
6.
An. bras. dermatol ; 97(3): 362-365, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1383584

ABSTRACT

Abstract Anogenital herpes is one of the most prevalent sexually transmitted infections worldwide. It has several clinical manifestations, from cases of primary herpes infection to recurrent forms, among them chronic mucocutaneous herpes. This presentation is rare, characterized by a duration of more than four weeks, usually associated with immunosuppression and resistance to classic anti-herpetic treatment. The present study presents a series of ten cases of chronic mucocutaneous herpes with a discussion about its clinical, laboratory, and therapeutic aspects.

7.
Journal of Clinical Hepatology ; (12): 328-333, 2022.
Article in Chinese | WPRIM | ID: wpr-920879

ABSTRACT

Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone ( P =0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.

8.
Article in Chinese | WPRIM | ID: wpr-920546

ABSTRACT

Upper respiratory tract is directly connected with the external environment, and its natural immune system is the first line of defense against pathogens. In antiviral infection, interferon (IFN) is the main component of the antiviral natural immune system and IFN-λ is a newly discovered immune effector molecule that is mainly produced in the mucosal barrier. IFN-λ exerts a biological role through Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathway, and plays an important part in regulating innate and acquired immunity of respiratory mucosa. IFN-λ principally expresses on the mucosal barrier with a long-lasting antiviral impact and controls immune-inflammatory damage, which is becoming a new focus of antiviral immunity research in the upper respiratory tract, especially in fighting against 2019 novel coronavirus diseases (COVID-19). Thus, we summarize the research progress of IFN-λ antiviral immunity in the upper respiratory tract to provide new insight in the prevention and treatment of viral infection in the upper respiratory tract.

9.
Article in Chinese | WPRIM | ID: wpr-913158

ABSTRACT

Objective To investigate the clinical effect of direct-acting antiviral agent (DAA) in the treatment of chronic hepatitis C (CHC) patients with thrombocytopenia and its effect on platelet count (PLT). Methods A retrospective analysis was performed for 83 CHC patients with thrombocytopenia (PLT 100×10 9 /L at baseline had a greater increase in PLT( P < 0.05). Conclusion CHC patients with thrombocytopenia have significant improvements in liver function and LSM after receiving DAA treatment and obtaining SVR12, and baseline LSM is an independent predictive factor for PLT elevation. There is a significant increase in PLT from baseline to EOT and SVR12.

10.
Acta Pharmaceutica Sinica B ; (6): 532-557, 2022.
Article in English | WPRIM | ID: wpr-929313

ABSTRACT

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

11.
Acta Pharmaceutica Sinica B ; (6): 511-531, 2022.
Article in English | WPRIM | ID: wpr-929312

ABSTRACT

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

12.
Acta Pharmaceutica Sinica B ; (6): 1636-1651, 2022.
Article in English | WPRIM | ID: wpr-929276

ABSTRACT

SARS-CoV-2 main protease (Mpro) is one of the most extensively exploited drug targets for COVID-19. Structurally disparate compounds have been reported as Mpro inhibitors, raising the question of their target specificity. To elucidate the target specificity and the cellular target engagement of the claimed Mpro inhibitors, we systematically characterize their mechanism of action using the cell-free FRET assay, the thermal shift-binding assay, the cell lysate Protease-Glo luciferase assay, and the cell-based FlipGFP assay. Collectively, our results have shown that majority of the Mpro inhibitors identified from drug repurposing including ebselen, carmofur, disulfiram, and shikonin are promiscuous cysteine inhibitors that are not specific to Mpro, while chloroquine, oxytetracycline, montelukast, candesartan, and dipyridamole do not inhibit Mpro in any of the assays tested. Overall, our study highlights the need of stringent hit validation at the early stage of drug discovery.

13.
Acta Pharmaceutica Sinica B ; (6): 581-599, 2022.
Article in English | WPRIM | ID: wpr-929274

ABSTRACT

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

14.
Article in Chinese | WPRIM | ID: wpr-928061

ABSTRACT

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.


Subject(s)
Animals , Chlorocebus aethiops , Drugs, Chinese Herbal/pharmacology , Enterovirus A, Human/physiology , Hand, Foot and Mouth Disease , Vero Cells
15.
Journal of Clinical Hepatology ; (12): 1165-1168, 2022.
Article in Chinese | WPRIM | ID: wpr-924800

ABSTRACT

Antiviral therapy can reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. As for the first-line antiviral drugs, more studies have shown that tenofovir disoproxil fumarate may be better than entecavir in reducing the risk of HCC, especially among Asian patients; a limited number of studies have shown that tenofovir alafenamide fumarate may be better than tenofovir disoproxil fumarate in reducing the risk of HCC; interferon has a better effect than nucleos(t)ide analogues alone in reducing the risk of HCC. Among the currently available drugs, interferon combined with nucleos(t)ide analogues may be the best choice to reduce the risk of HCC in patients at a high risk of HCC. The level of evidence-based medicine is weak for comparing the effect of different drugs in reducing the risk of HCC, and randomized controlled trials are needed for further clarification. In practice, it is necessary to weigh the risk of HCC, drug tolerance and economic affordability based on the patient's basic conditions and actual situations, so as to develop individualized anti-viral strategies.

16.
Journal of Clinical Hepatology ; (12): 1059-1063, 2022.
Article in Chinese | WPRIM | ID: wpr-924776

ABSTRACT

Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.

17.
Acta Pharmaceutica Sinica ; (12): 1289-1300, 2022.
Article in Chinese | WPRIM | ID: wpr-924759

ABSTRACT

Virus infection is a serious threat to human health and social development. The increase in pandemics caused by emerging and re-emerging viruses highlights the urgent need for broad-spectrum antivirals. In this perspective, we highlight recent case studies and summarize the universal strategies and methodologies in broad-spectrum antiviral drug discovery from common targets, common steps in viral life cycle, universal strategies, and broad-spectrum molecules, hoping to provide valuable guidance for the current and future development of antiviral drugs.

18.
Journal of Clinical Hepatology ; (12): 1269-1274, 2022.
Article in Chinese | WPRIM | ID: wpr-924695

ABSTRACT

Objective To investigate the impact of the change in anti-hepatitis B virus (HBV) therapy indication on treatment rate and the features of the population requiring treatment. Methods The treatment-naïve patients with chronic hepatitis B (CHB) in the China Registry of Hepatitis B (CR-HepB) database were selected as subjects, and related demographic, virological, hematological, and biochemical data were collected. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results A total of 3640 treatment-naïve CHB patients were included in this study, among whom 64.4% were male, 68.7% had an age of 30-59 years, and 46.8% had an indeterminate clinical stage. According to the 2015 and 2019 editions of Guidelines for the prevention and treatment of chronic hepatitis B and the 2022 edition of expert consensus, the number of patients who had the indication for antiviral therapy was 625(17.2%), 1333(36.6%), and 2890(79.4%), respectively. The number of patients requiring treatment was increased by 1557 according to the 2022 edition of expert consensus, among whom 1424(91.5%) met the treatment threshold of alanine aminotransferase (ALT) > 30 U/L for male patients or ALT > 19 U/L for female patients. The additional patients requiring treatment according to the 2022 edition of expert consensus had significantly higher levels of ALT and HBV DNA and significantly lower scores of APRI and FIB-4 than the additional patients requiring treatment according to the 2019 edition of Guidelines (all P < 0.05). Conclusion The expansion of antiviral therapy indications for CHB may significantly increase the proportion of CHB patients receiving antiviral treatment and help mild CHB patients at the risk of disease progression to receive timely treatment and achieve the improvement in long-term prognosis.

19.
Journal of Clinical Hepatology ; (12): 541-546, 2022.
Article in Chinese | WPRIM | ID: wpr-922950

ABSTRACT

Objective To investigate the efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/c/F/TAF) combined with sofosbuvir/velpatasvir (SOF/VEL) in the treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and the changes in blood lipid levels. Methods This prospective cohort study was conducted among 10 previously untreated chronic hepatitis C patients with HIV/HCV co-infection who attended Department of Infectious Diseases in Tangdu Hospital from July 2019 to May 2021 and achieved continuous HIV suppression after antiretroviral treatment (ART). As for anti-HIV therapy, the ART regimen was switched to the E/c/F/TAF regimen for 32 weeks, and for anti-HCV therapy, the SOF/VEL regimen was started since week 4 after switching and lasted for 12 weeks. Related indices were monitored before and after switching to E/c/F/TAF for anti-HCV therapy and SOF/VEL for anti-HCV therapy, including body weight, body mass index, HCV genotype, alpha-fetoprotein, liver stiffness measurement, CD4 + T cell count, CD4 + T/CD8 + T ratio, hepatic and renal function parameters, blood lipids, HIV RNA, HCV RNA, SVR12, SVR24, and adverse reactions. The Mann-Whitney U test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was performed. Results After 4 weeks of treatment with E/c/F/TAF, 10 patients (HCV genotypes 2a and 1b) had HIV RNA below the lower limit of detection (20 IU/ml) and a significant reduction in albumin ( Z =-2.801, P =0.003 7), with the other indices remaining stable, and the patients reported significant improvements in the adverse events of anti-HIV therapy with the former ART regimen. After 4 weeks of E/c/F/TAF combined with SOF/VEL, the patients had HCV RNA below the lower limit of detection (15 IU/ml), and both SVR12 and SVR24 reached 100%; after 12 weeks of anti-HCV therapy, there were significant reductions in alanine aminotransferase ( Z =-2.732, P =0.004 8) and aspartate aminotransferase ( Z =-2.501, P =0.010 7) and significant increases in total cholesterol (TC) ( Z =-2.797, P =0.003 9) and low-density lipoprotein cholesterol (LDL-C) ( Z =-2.343, P =0.018 5), with a significantly positive correlation between them ( r =0.87, P < 0.001), and all the other indices were normal. Conclusion For previously untreated chronic hepatitis C patients with HIV/HCV co-infection, switching to E/c/F/TAF combined with SOF/VEL has good efficacy, tolerability, and safety, and the combination of the two regimens can avoid drug interaction, achieve a high HCV cure rate, and maintain HIV suppression. Transient increases in TC and LDL-C are observed during combination treatment, which suggests dyslipidemia caused by HCV infection and the pharmacological action of this regimen.

20.
Acta Pharmaceutica Sinica ; (12): 576-592, 2022.
Article in Chinese | WPRIM | ID: wpr-922887

ABSTRACT

Over the course of human civilization, viral infections have been a part of human life and still represent one of the heaviest burdens for human and society, with a huge devastating socioeconomic impact. Inorganic and bioinorganic chemistry have made important contributions to medical science and human health in the past half century. In this paper, we selected the representative cases in recent years, and reviewed the research progress of antiviral drug discovery from the perspective of bioinorganic chemistry.

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