DrugVirus.info 2.0 : an integrative data portal for broad-spectrum antivirals (BSA) and BSA-containing drug combinations (BCCs)

Viruses can cross species barriers and cause unpredictable outbreaks in man with substantial economic and public health burdens. Broad-spectrum antivirals, (BSAs, compounds inhibiting several human viruses), and BSA-containing drug combinations (BCCs) are deemed as immediate therapeutic options that fill the void between virus identification and vaccine development. Here, we present DrugVirus.info 2.0 (https://drugvirus.info), an integrative interactive portal for exploration and analysis of BSAs and BCCs, that greatly expands the database and functionality of DrugVirus.info 1.0 webserver. Through the data portal that now expands the spectrum of BSAs and provides information on BCCs, we developed two modules for (i) interactive analysis of users' own antiviral drug and combination screening data and their comparison with published datasets, and (ii) exploration of the structure-activity relationship between various BSAs. The updated portal provides an essential toolbox for antiviral drug development and repurposing applications aiming to identify existing and novel treatments of emerging and re-emerging viral threats. [GRAPHICS] .Peer reviewe

Active Components of Commonly Prescribed Medicines Affect Influenza A Virus-Host Cell Interaction : A Pilot Study

Background: Every year, millions of people are hospitalized and thousands die from influenza A virus (FLUAV) infection. Most cases of hospitalizations and death occur among the elderly. Many of these elderly patients are reliant on medical treatment of underlying chronic diseases, such as arthritis, diabetes, and hypertension. We hypothesized that the commonly prescribed medicines for treatment of underlying chronic diseases can affect host responses to FLUAV infection and thus contribute to the morbidity and mortality associated with influenza. Therefore, the aim of this study was to examine whether commonly prescribed medicines could affect host responses to virus infection in vitro. Methods: We first identified 45 active compounds from a list of commonly prescribed medicines. Then, we constructed a drug-target interaction network and identified the potential implication of these interactions for FLUAV-host cell interplay. Finally, we tested the effect of 45 drugs on the viability, transcription, and metabolism of mock- and FLUAV-infected human retinal pigment epithelial (RPE) cells. Results: In silico drug-target interaction analysis revealed that drugs such as atorvastatin, candesartan, and hydroxocobalamin could target and modulate FLUAV-host cell interaction. In vitro experiments showed that at non-cytotoxic concentrations, these compounds affected the transcription and metabolism of FLUAV- and mock-infected cells. Conclusion: Many commonly prescribed drugs were found to modulate FLUAV-host cell interactions in silico and in vitro and could therefore affect their interplay in vivo, thus contributing to the morbidity and mortality of patients with influenza virus infections.Peer reviewe

Seven classes of antiviral agents

The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we briefly reviewed 7 classes of antiviral agents: neutralizing antibodies, neutralizing recombinant soluble human receptors, antiviral CRISPR/Cas systems, interferons, antiviral peptides, antiviral nucleic acid polymers, and antiviral small molecules. Interferons and some small molecules alone or in combinations possess broad-spectrum antiviral activity, which could be beneficial for treatment of emerging and re-emerging viral infections.Peer reviewe

Novel Synergistic Anti-Enteroviral Drug Combinations

Background: Enterovirus infections affect people around the world, causing a range of illnesses, from mild fevers to severe, potentially fatal conditions. There are no approved treatments for enterovirus infections. Methods: We have tested our library of broad-spectrum antiviral agents (BSAs) against echovirus 1 (EV1) in human adenocarcinoma alveolar basal epithelial A549 cells. We also tested combinations of the most active compounds against EV1 in A549 and human immortalized retinal pigment epithelium RPE cells. Results: We confirmed anti-enteroviral activities of pleconaril, rupintrivir, cycloheximide, vemurafenib, remdesivir, emetine, and anisomycin and identified novel synergistic rupintrivir-vemurafenib, vemurafenib-pleconaril and rupintrivir-pleconaril combinations against EV1 infection. Conclusions: Because rupintrivir, vemurafenib, and pleconaril require lower concentrations to inhibit enterovirus replication in vitro when combined, their cocktails may have fewer side effects in vivo and, therefore, should be further explored in preclinical and clinical trials against EV1 and other enterovirus infections.Peer reviewe

Influenza pH1N1 virus accumulated H275Y mutation neuraminidase during propagation in MDCK cells

Peer reviewe

Ivermectin effectively inhibits hepatitis E virus replication, requiring the host nuclear transport protein importin α1

We show that ivermectin, an FDA-approved anti-parasitic drug, effectively inhibits infection with hepatitis E virus (HEV) genotypes 1 and 3 in a range of cell culture models, including hepatic and extrahepatic cells. Long-term treatment showed no clear evidence of the development of drug resistance. Gene silencing of importin-α1, a cellular target of ivermectin and a key member of the host nuclear transport complex, inhibited viral replication and largely abolished the anti-HEV effect of ivermectin.</p

Ivermectin effectively inhibits hepatitis E virus replication, requiring the host nuclear transport protein importin α1

We show that ivermectin, an FDA-approved anti-parasitic drug, effectively inhibits infection with hepatitis E virus (HEV) genotypes 1 and 3 in a range of cell culture models, including hepatic and extrahepatic cells. Long-term treatment showed no clear evidence of the development of drug resistance. Gene silencing of importin-α1, a cellular target of ivermectin and a key member of the host nuclear transport complex, inhibited viral replication and largely abolished the anti-HEV effect of ivermectin.</p