Abstract:Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal outbreaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treatment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some references for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development.Keywords: influenza virus; chemosynthetic drugs; plant extracts; microbial metabolites; drug resistance
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The WHO developed a blueprint of potential therapeutic candidates in January 2020. WHO has embarked on an ambitious global "megatrial" called SOLIDARITY in which confirmed cases of COVD-19 are randomized to standard care or one of four active treatment arms (remdesivir, chloroquine or hydroxychloroquine, lopinavir/ritonavir, or lopinavir/ritonavir plus interferon beta-1a). In early July 2020, the treatment arms in hospitalized patients that included hydroxychloroquine, chloroquine, or lopinavir/ritonavir were discontinued owing to the drugs showed little or no reduction in mortality compared with standard of care. [13] Interim results released mid-October 2020 found the four aforementioned repurposed antiviral agents appeared to have little or no effect on hospitalized patients with COVID-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. The 28-day mortality was 12% (39% if already ventilated at randomization, 10% otherwise). [14]
Oral synthetic retinoid shown to address the complex links between fatty acids metabolism and inflammatory signaling, which is distinct from the retinoid class MOA. Believed to work by modulating key membrane lipids in conjunction with proinflammatory pathways (eg, ERK1/2, NF-kappa-B, and cPLA2) needed for coronavirus entry, replication, and host defense evasion. It may also have antiviral properties. The phase 2 RESOLUTION trial did not meet its primary endpoint of improving the proportion of patients alive and free of respiratory failure on Day 29 in patients with moderate, severe, or critical COVID-19 disease. However, LAU-7b showed 100% reduction in risk of progression to mechanical ventilation and death in moderate-to-sever disease. Phase 3 portion of the RESOLUTION study in hospitalized patients with moderate-to-severe COVID-19 commenced February 2022.
Analysis of patients who remained in respiratory failure despite treatment with remdesivir identified a statistically significant (P = .03) 2.5-fold increased odds of being alive and free of respiratory failure and a statistically significant (P = .006) 4-fold higher odds of being alive at Day 60 among patients treated with aviptadil compared with those treated with placebo. Although antiviral treatment has shown advantages in treating patients with earlier stages of COVID-19, aviptadil is the first to demonstrate increased recovery and survival in patients who have already progressed to respiratory failure. [107]
Organoids have great potential for high-throughput applications, but the lack of standardization hinders their inclusion, with the relatively long differentiation times and the reliance on ECMs further aggravating the situation. Here, we describe a novel ECM-free method to generate apical-out airway organoids (Ap-O AO) by differentiating aggregates derived from 2D-expanded human bronchial epithelial cells (hBECs). The complete absence of ECM and the use of micropatterned plates followed by suspension culture, can overcome the obstacles that ECM-embedded airway organoids face, and may allow the utilization of Ap-O AO in high-throughput assays such as antiviral drug screenings. For this purpose, we show infectivity of the Ap-O AO by respiratory viruses as well as inhibition of viral replication by antivirals.
In conclusion, we have generated an ECM-free workflow that allows the efficient generation of airway organoids that expose their apical side to the media. These organoids are susceptible to infection with a variety of viruses targeting the human airway epithelium and can be utilized to assess the effect of antivirals in virus replication. The absence of an animal-derived ECM scaffold, the high efficiency and the relative short duration of the assay, offers the opportunity to scale up this method in a cost-effective manner and make it suitable for ultra-high-throughput downstream applications in the context of both infectious and other disease modelling.
5. Mashiba T, Joko K, Kurosaki M, Ochi H, Osaki Y, et al. Does interferon-free direct-acting antiviral therapy for hepatitis c after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of hcc? A multicenter study by the Japanese red cross hospital liver study group. PLoS One 2018;13:e0194704.
43. Cardoso H, Vale AM, Rodrigues S, Gonçalves R, Albuquerque A, et al. High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis. J Hepatol 2016;65:1070-1.
In this section are the practice problems and questions for nursing pharmacology. There are 530+ nursing pharmacology practice questions in this nursing test bank partitioned into 11 parts. Nursing topics include medication administration, dosage calculations, general concepts about nursing pharmacology, cardiovascular drugs, antibiotics and anti-infectives, neurological medications, psychiatric medications, drugs for the respiratory system, gastrointestinal system, and endocrine system. 2ff7e9595c
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