Biology subjects

Vitkauskiene, A.

Publications and source records attributed to Vitkauskiene, A..

3 recordsLinked to original sources

bioRxiv2022

Broad-spectrum mono- and combinational drug therapies for global viral pandemic preparedness

Broadly effective antiviral therapies must be developed to be ready for clinical trials, which should begin soon after the emergence of new life-threatening viruses. Here, we pave the way towards this goal by analyzing conserved druggable virus-host interactions, mechanisms of action and immunomodulatory properties of broad-spectrum antivirals (BSAs), routes of BSA delivery, and BSA interactions with other antivirals. Based on the analysis we developed scoring systems, which allowed us to predict novel BSAs and BSA-containing drug combinations (BCCs). Thus, we have developed a new strategy to broaden the spectrum of BSA indications and predict novel mono-and combinational therapies that can help better prepare for imminent future viral outbreaks. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/476444v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@7fee8dorg.highwire.dtl.DTLVardef@1069131org.highwire.dtl.DTLVardef@2632bforg.highwire.dtl.DTLVardef@1cdcbf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2020

Identification of novel antiviral drug combinations in vitro and tracking their development

Combination therapies have become a standard for the treatment for HIV and HCV infections. They are advantageous over monotherapies due to better efficacy and reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify several new synergistic combinations against emerging and re-emerging viral infections in vitro. We observed synergistic activity of nelfinavir with investigational drug EIDD-2801 and convalescent serum against SARS-CoV-2 infection in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of vemurafenib combination with emetine, homoharringtonine, gemcitabine, or obatoclax against echovirus 1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar and niclosamide were synergistic against HCV infection in hepatocyte derived Huh-7.5 cells, whereas combinations of monensin with lamivudine and tenofovir were synergistic against HIV-1 infection in human cervical TZM-bl cells. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Overall, the development of combinational therapies could have a global impact improving the preparedness and protection of the general population from emerging and re-emerging viral threats.

microbiology↗

bioRxiv2019

Critical Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis

Viruses are one of the major causes of various acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signalling pathways. A collective view of these multiple studies could advance our understanding of viral evasion mechanisms and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.

immunology↗