Curtailing virus-induced inflammation in respiratory infections: emerging strategies for therapeutic interventions

Abstract

Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections. XC221GI is capable of controlling IFN-gamma-driven inflammation as it is evident from the suppression of the production of soluble cytokines and chemokines, including IL-6, IL-8, CXCL10, CXCL9 and CXCL11 as well as a decrease in migration of neutrophils into the pulmonary tissue. An excellent safety profile of XC221GI, which is not metabolized by the liver, and its significant anti-inflammatory effects indicate utility of this compound in abating conversion of ambulatory cases of respiratory infections into the cases with aggravated presentation that require hospitalization. This drug is especially useful when rapid molecular assays determining viral species are impractical, or when direct antiviral drugs are not available. Moreover, XC221GI may be combined with direct antiviral drugs to enhance their therapeutic effects.

Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19

“…In this unit, IFN-γ, a pleiotropic cytokine with roles in a variety of biological responses including protection from viral and bacterial infections, induces both CXCL11 and CCL4 ( 27 ), and, by doing that, promotes cytokine storm. In some antiviral therapeutic approaches, co-inducible inflammatory cytokines are even treated as a collective pharmacological target ( 28 ). When, at the inception of the disease, levels of both the IFN-γ and the secondary cytokines/chemokines are too low, such as pre-existing suppression, the inflammatory cascade response intended to counteract viral replication may develop further after a certain delay, and eventually progress to a detrimental extent ( 29 ).…”

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

“…За этот период создана многоуровневая экспериментальная доказательная база, подтверждающая эффективность препарата в отношении целого ряда вирусных инфекций (гриппа, респираторно-синцитиальной, коронавирусной, риновирусной, аденовирусной и др. ), а также раскрывающая механизм действия препарата на молекулярном и клеточном уровнях [3]. Установлено, что Атериксен® снижает выработку провоспалительных цитокинов и хемокинов, ассоциированных с развитием вирусного воспаления в дыхательных путях.…”

Experience in using Aterixen® in clinical practice. Results of the "SUPRA" observation program

“…Эффективность и безопасность препарата продемонстрированы в ряде доклинических и клинических исследований [1]. В частности, установлено, что основноепротивовоспалительное -фармакологическое действие препарата реализуется за счет влияния на выработку провоспалительных цитокинов интерлейкина (ИЛ)-6, 8 и хемокинов IP-10 (CXCL10), MIG (CXCL9), которые являются ведущими медиаторами острой фазы воспаления, лихорадки и цитокинового шторма [2].…”