Antiviral Therapy for the Next Influenza Pandemic

Hurt, Aeron C.

doi:10.3390/tropicalmed4020067

Cited by 25 publications

(30 citation statements)

References 23 publications

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“…Neuraminidase is a validated drug target and several small molecules that inhibit its activity are licensed as influenza therapeutics (32). Of note, in this work several attempts to generate H3N2 escape mutants were unsuccessful.…”

Section: One Sentence Summarymentioning

confidence: 99%

Broadly protective human antibodies that target the active site of influenza virus neuraminidase

Stadlbauer

Zhu

McMahon

et al. 2019

Science

187

207

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Better vaccines against influenza virus are urgently needed to provide broader protection against diverse strains, subtypes, and types. Such efforts are assisted by the identification of novel broadly neutralizing epitopes targeted by protective antibodies. Influenza vaccine development has largely focused on the hemagglutinin, but the other major surface antigen, the neuraminidase, has reemerged as a potential target for universal vaccines. We describe three human monoclonal antibodies isolated from an H3N2-infected donor that bind with exceptional breadth to multiple different influenza A and B virus neuraminidases. These antibodies neutralize the virus, mediate effector functions, are broadly protective in vivo, and inhibit neuraminidase activity by directly binding to the active site. Structural and functional characterization of these antibodies will inform the development of neuraminidase-based universal vaccines against influenza virus.

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Section: One Sentence Summarymentioning

confidence: 99%

Broadly protective human antibodies that target the active site of influenza virus neuraminidase

Stadlbauer

Zhu

McMahon

et al. 2019

Science

187

207

View full text Add to dashboard Cite

show abstract

“…Even when vaccines are in widespread use against viruses, for example influenza, their effectiveness can vary markedly ( 1 ) and protection cannot be guaranteed. Similarly, antiviral drugs are not available for all viruses; some that are effective against influenza virus can be used prophylactically ( 2 ), but their window of protection is short and ongoing use is not recommended because of the potential for the selection of drug-resistant variants ( 3 ). Furthermore, because most antiviral agents are specific to a particular virus family or genus, they may not be appropriate for unrelated endemic or emerging viruses.…”

Section: Introductionmentioning

confidence: 99%

TLR2-mediated activation of innate responses in the upper airways confers antiviral protection of the lungs

Deliyannis¹,

Wong²,

McQuilten³

et al. 2021

JCI Insight

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The impact of respiratory virus infections on global health is felt not just during a pandemic but for many, endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen independent innate immunity in the upper airways can prevent spread of respiratory virus infection to the vulnerable lower airways. Activation of toll-like receptor-2 (TLR2), when restricted to the nasal turbinates results in prompt induction of innate immune-driven anti-viral responses through action of cytokines, chemokines and cellular activity in the upper but not the lower airways. We define how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to seven days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and also support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

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“…However, the threat posed by influenza pandemics is ever present and anti-influenza drugs are stockpiled by individual governments as part of their pandemic preparedness plans. 4 Thus, with the exception of HIV/AIDS, Influenza and now COVID-19, most of the viral diseases on the WHO list of global health threats can be considered to be ''neglected viral diseases''. 25…”

Section: Antiviral Strategiesmentioning

confidence: 99%

“…2,3 While planning for an influenza pandemic is an ongoing global priority, the 2014 EBOV disease (EBVD) outbreak in West Africa and the emergence in 2015 of ZIKV-caused diseases in Brazil that spread rapidly to 84 countries around the world are a stark warning of the potential threat and the lack of preparedness for dealing with RNA virus outbreaks. [4][5][6] The SARS-CoV-2/COVID-19 pandemic has further exposed the lack of antiviral compounds that can be rapidly mobilized and deployed for the treatment of re-emerging or emerging viral diseases. 7 Here we review the current status of antiviral therapies, highlighting strategies for combatting EBOVcausing disease (EBOD) and COVID-19, targets for antiviral drug discovery and discuss the challenges, solutions and options to accelerate antiviral drug discovery efforts.…”

Section: Introductionmentioning

confidence: 99%