Emerging drug design strategies in anti-influenza drug discovery

Liu, Chuanfeng; Hu, Lide; Dong, Guofeng; Zhang, Ying; Silva-Júnior, Edeildo Ferreira da; Liu, Xinyong; Menéndez‐Arias, Luis; Zhan, Peng

doi:10.1016/j.apsb.2023.08.010

Cited by 8 publications

(3 citation statements)

References 124 publications

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“…Influenza is a global infectious disease caused by a single stranded negative sense RNA virus named influenza virus, which is Liu et al (2023) . According to the statistical data of World Health Organization, seasonal influenza epidemics cause an estimated 3 to 5 million cases of severe cases worldwide, resulting in approximately 500,000 deaths, and causing significant economic losses and social burdens ( Eichberg et al, 2022 ).…”

Section: Akkermansia Muciniphila and Infection Related Diseasesmentioning

confidence: 99%

Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases

Li,

Chen

et al. 2024

Front. Microbiol.

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Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3–5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.

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Section: Akkermansia Muciniphila and Infection Related Diseasesmentioning

confidence: 99%

Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases

Li,

Chen

et al. 2024

Front. Microbiol.

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“…As severe influenza infection involves an exacerbation of the inflammatory response, which is influenced by both viral and host‐related factors, the use of immunomodulators or compounds targeting the immune response of the host could be clinically very advantageous. This justifies the continued efforts of researchers to develop novel anitivirals and immunomodulatory compounds with some drug candidates being at different clinical stages of development 9 . In that regard, the protectins constitute a family of specialized pro‐resolving mediators which are endogenous bioactive products formed during the resolution phase of acute inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…This justifies the continued efforts of researchers to develop novel anitivirals and immunomodulatory compounds with some drug candidates being at different clinical stages of development. 9 In that regard, the protectins constitute a family of specialized pro-resolving mediators which are endogenous bioactive products formed during the resolution phase of acute inflammation. They further contribute to enhance the return of inflamed/injured tissue to homeostasis.…”

mentioning

confidence: 99%

A protectin DX (PDX) analog with in vitro activity against influenza A(H1N1) viruses

Fortin,

Hénaut,

Goyette

et al. 2024

Journal of Medical Virology

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Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro‐resolving mediators, have previously demonstrated anti‐influenza activity as well as anti‐inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir‐ and baloxavir‐resistant variants. In ST6GalI‐MDCK cells, the PDX analog AN‐137B reduced viral replication in a dose‐dependent manner with IC50 values of 23.8 for A/Puerto Rico/8/1934 (H1N1) and between 32.6 and 36.7 µM for susceptible and resistant A(H1N1)pdm09 viruses. In MTS‐based cell viability experiments, AN‐137B showed a 50% cellular cytotoxicity (CC50) of 638.7 µM with a resulting selectivity index of 26.8. Of greater importance, the combination of AN‐137B with oseltamivir or baloxavir resulted in synergistic and additive in vitro effects, respectively. Treatment of lipopolysaccharide (LPS)‐stimulated macrophages with AN‐137B resulted in a decrease of iNOS activity as shown by the reduction of nitrite production, suggesting an anti‐inflammatory effect. In conclusion, our results indicate that the protectin analog AN‐137B constitutes an interesting therapeutic modality against influenza A virus, warranting further evaluation in animal models.

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