Modulation of the Host Response as a Therapeutic Strategy in Severe Lung Infections

Abstract

Respiratory pathogens such as influenza and SARS-CoV-2 can cause severe lung infections leading to acute respiratory distress syndrome (ARDS). The pathophysiology of ARDS includes an excessive host immune response, lung epithelial and endothelial cell death and loss of the epithelial and endothelial barrier integrity, culminating in pulmonary oedema and respiratory failure. Traditional approaches for the treatment of respiratory infections include drugs that exert direct anti-pathogen effects (e.g., antivirals). However, such agents are typically ineffective or insufficient after the development of ARDS. Modulation of the host response has emerged as a promising alternative therapeutic approach to mitigate damage to the host for the treatment of respiratory infections; in principle, this strategy should also be less susceptible to the development of pathogen resistance. In this review, we discuss different host-targeting strategies against pathogen-induced ARDS. Developing therapeutics that enhance the host response is a pathogen-agnostic approach that will help prepare for the next pandemic.

Genome-wide CRISPR activation screen identifies JADE3 as an antiviral activator of NF-kB–dependent IFITM3 expression

“…This includes IAV with NS1 known to modulate NF-kB signaling as well as inhibiting IFITM3 expression ( 64 , 65 , 66 ). Furthermore, overactivation of the pathway has been implicated in the pathogenesis of multiple viruses, where damage is often due to over-active inflammatory host damage ( 67 ). The increased expression of many NF-kB–related genes in JADE3 overexpression and JADE3 KO cells suggests a complicated balancing of NF-kB signaling by JADE3.…”

Aesculus hippocastanum extract and the main bioactive constituent β-escin as antivirals agents against coronaviruses, including SARS-CoV-2

“…Meanwhile, for SARS-CoV-2, therapeutic agents include ritonavir-boosted nirmatrelvir (Paxlovid), remdesivir, and molnupiravir. However, antiviral drugs may cause resistance by exerting selective pressure on the pathogen 1 , 2 . Despite the differences in host response to viral infections, the downstream effects are often the same, resulting in excessive inflammation and a loss of lung barrier integrity, which can lead to oedema and tissue damage 1 .…”

“…However, antiviral drugs may cause resistance by exerting selective pressure on the pathogen 1 , 2 . Despite the differences in host response to viral infections, the downstream effects are often the same, resulting in excessive inflammation and a loss of lung barrier integrity, which can lead to oedema and tissue damage 1 . Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections.…”

“…Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections. The recent COVID-19 pandemic has made clear that this approach may be valuable, as treatment with corticosteroids such as dexamethasone has a significant impact on outcomes 1 , 3 .…”

Application of HS221GI in treatment of influenza and ARVI in adults: a new approach – managing virus-induced inflammation. Results of a double-blind, randomized, placebo-controlled, multicenter clinical trial

“…Таким образом, препаратом контролируется ключевая мишень клеток организма человека, эксплуатируемая респираторными вирусами в ходе реализации их жизненного цикла, сопровождающегося цитопатическим действием с исходом в ВИВ. Данная особенность механизма действия препарата Атериксен® отражает инновационную стратегию управления инфекционным процессом на уровне мишеней клеток хозяина (host response strategy), не сопряженную с рисками запуска эволюционных процессов резистентности, характерными для препаратов, воздействующих на мишени вируса, и поэтому представляет значительный интерес для эмпирического применения в клинической практике [5][6][7].…”