iDMer: an integrative and mechanism-driven response system for identifying compound interventions for sudden virus outbreak

Abstract

Emerging viral infections seriously threaten human health globally. Several challenges exist in identifying effective compounds against viral infections: (1) at the initial stage of a new virus outbreak, little information, except for its genome information, may be available; (2) although the identified compounds may be effective, they may be toxic in vivo and (3) cytokine release syndrome (CRS) triggered by viral infections is the primary cause of mortality. Currently, an integrative tool that takes all those aspects into consideration for identifying effective compounds to prevent viral infections is absent. In this study, we developed iDMer, as an integrative and mechanism-driven response system for addressing these challenges during the sudden virus outbreaks. iDMer comprises three mechanism-driven compound identification modules, that is, a virus-host interaction-oriented module, an autophagy-oriented module and a CRS-oriented module. As a one-stop integrative platform, iDMer incorporates compound toxicity evaluation and compound combination identification for virus treatment with clear mechanisms. iDMer was successfully tested on five viruses, including the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results indicated that, for all five tested viruses, compounds that were reported in the literature or experimentally validated for virus treatment were enriched at the top, demonstrating the generalized effectiveness of iDMer. Finally, we demonstrated that combinations of the individual modules successfully identified combinations of compounds effective for virus intervention with clear mechanisms.

Identification of common genes and pathways between type 2 diabetes and COVID-19

“…Therefore, COPS3 may regulate the development of T2DM through the Raf-1/MEK/ERK signaling pathway and autophagy regulation. Additionally, SARS-CoV-2 can hinder autophagy by blocking autophagosome-lysosome fusion ( Miao et al, 2021 ), and activation of autophagy can inhibit the replication and spread of SARS-CoV-2 ( Gassen et al, 2021 ; Wei et al, 2021 ). Thus, COPS3 may regulate the development of COVID-19 by modulating autophagy.…”

Targets and mechanisms of Alpinia oxyphylla Miquel fruits in treating neurodegenerative dementia

“…ProTox-II extracts various toxicological parameters from the compounds’ SMILES representation to predict acute oral toxicity (LD50, mg/kg) and several toxicity end points, including carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity, and it ranks the acute toxicity of each compound in six classes, namely, Fatal (Class-1), Fatal (Class-2), Toxic (Class-3), Harmful (Class-4), May be harmful (Class-5), and Non-toxic (Class-6). According to previous research ( Wei et al, 2021 ), a compound in an acute toxicity class lower than Class-3 and with more than three active toxicity end points is considered to be toxic.…”

Liuwei Dihuang Pills in the Treatment of Senile Dementia: A Review

“…ProTox-II classifies the acute toxicity of each compound from 1 to 6, corresponding to lethal, lethal, toxic, harmful, possibly harmful, and non-toxic. According to literature [40,41]， compounds with acute toxicity levels below grade 3 and greater than three positive toxicity endpoints are considered toxic. Therefore, 35 components of LWDHP were non-toxic, among which 15 components had no positive toxicological end points, 6 components had 2 positive toxicological end points, and 14 components had 1 positive toxicological end point (Figure 1).…”