Denis E Kainov

Denis E Kainov
University of Helsinki | HY

PhD

About

119
Publications
18,561
Reads
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2,793
Citations
Citations since 2017
66 Research Items
1952 Citations
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Introduction
Denis Kainov received his PhD in Genetics from the University of Helsinki in 2005. He performed his postdoctoral training in IGBMC, France and in CRP-Sante, Luxembourg during 2005-2009. He then returned to Finland, and started his independent career as a FIMM-EMBL group leader in 2010.
Additional affiliations
November 2009 - present
Institute for Molecular Medicine, Finland
Position
  • Group Leader
December 2007 - November 2009
LIH Luxembourg Institute of Health
Position
  • PostDoc Position
December 2005 - November 2007

Publications

Publications (119)
Article
Full-text available
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 reviewing conserved druggable virus-host interactions, mechanisms of action and immunomodulatory properties of available broad-spectrum antiv...
Article
Full-text available
COVID-19 pandemic continues to remain a global health concern due to the emergence of newer variants. Several multiOmics studies have produced extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regulated by post-translational modifications and their...
Article
Full-text available
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 solu...
Article
Full-text available
Our Special Issue received a great deal of attention, and several important papers have recently been added to it. Thus, we are pleased to extend our previous Editorial [1] and to highlight all the papers of the issue. In this Special Issue, several papers are focused on broad-spectrum antivirals (BSAs). BSAs could be referred to as antivirals that...
Article
Full-text available
Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infectio...
Article
Full-text available
Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infectio...
Preprint
Full-text available
Despite the availability of vaccines and approved therapeutics, the COVID-19 pandemic continues to rise owing to the emergence of newer variants. Several multi-omics studies have made available extensive evidence on host-pathogen interactions and potential therapeutic targets. Nonetheless, an increased understanding of host signaling networks regul...
Article
Full-text available
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 alveol...
Preprint
Full-text available
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 alveo...
Preprint
Full-text available
Background: Some viruses cause outbreaks which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, development of mon-oclonal antibodies is often long, laborious, and unprofitable. Here we report a Norwegian platform for development of chicken polyclonal neutralizing antibodies with powerf...
Article
Full-text available
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 va...
Article
Full-text available
Viral diseases consistently pose a substantial economic and public health burden worldwide. This burden is due to the viruses’ ability to be transmitted from wild and domestic animals to humans, resulting in unpredictable outbreaks [1]. The current strategy for viral outbreak management is heavily reliant on vaccines and antiviral treatments [2]. W...
Article
Full-text available
A middle-aged woman tested negative for SARS-CoV-2 upon arrival after an international flight. She had been vaccinated with two doses of mRNA vaccine several weeks before and was routinely quarantined together with two of her children traveling together. On day 7 she tested positive by PCR with a very high virus load (Ct value 13.4, 10 7copies / ml...
Article
Hepatotropic viruses naturally have narrow host and tissue tropisms, challenging the development of robust experimental models. The advent of organoid technology provides a unique opportunity for moving the field forward. Here, we demonstrate that three-dimensional cultured organoids from fetal and adult human liver with cholangio-cyte or hepatocyt...
Preprint
Full-text available
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 (BSA...
Article
Full-text available
The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We p...
Article
Full-text available
The world was unprepared for coronavirus disease 2019 (COVID-19) and remains ill-equipped for future pandemics. While unprecedented strides have been made developing vaccines and treatments for COVID-19, there remains a need for highly effective and widely available regimens for ambulatory use for novel coronaviruses and other viral pathogens. We p...
Preprint
Full-text available
Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome c...
Article
Full-text available
Background: There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. Methods: Here, we tested the antiviral properties of interferons (IFNs), alone and with other drugs in vitro. Results: While IFNs alone were insufficient to completely abolish replication of severe acute respiratory syndrome corona...
Article
Full-text available
SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results...
Article
Full-text available
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...
Article
Emerging and re-emerging viral diseases occur with regularity within the human population. The conventional ‘one drug, one virus’ paradigm for antivirals does not adequately allow for proper preparedness in the face of unknown future epidemics. In addition, drug developers lack the financial incentives to work on antiviral drug discovery, with most...
Preprint
Full-text available
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 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...
Preprint
Full-text available
SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here we address these challenges by combining Pegasys (IFNa) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results...
Article
Full-text available
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...
Article
Full-text available
Background & Aims Chronic hepatitis B is an incurable disease. Addressing the unmet medical need for therapies has been hampered by a lack of suitable cell culture models to investigate the HBV life cycle in a single experimental setup. We sought to develop a platform suitable to investigate all aspects of the entire HBV life cycle. Methods HepG...
Article
Full-text available
Therapeutic options for coronaviruses remain limited. To address this unmet medical need, we screened 5406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 ha...
Article
Full-text available
Objective: The aim of the present study was repositioning of ivermectin in treatment of gastric cancer (GC) by computational prediction based on gene expression profiles of human and mouse model of GC and validations with in silico , in vitro and in vivo approaches. Methods: Computational drug repositioning was performed using connectivity map (cMa...
Article
Full-text available
Tumors comprise cancer cells and the associated stromal and immune/inflammatory cells, i.e., tumor microenvironment (TME). Here, we identify a metabolic signature of human and mouse model of gastric cancer, and show that vagotomy in the mouse model reverses the metabolic reprogramming, reflected by metabolic switch from glutaminolysis to OXPHOS/gly...
Article
Full-text available
DNA in our cells is constantly modified by internal and external factors. For example, metabolic byproducts, ionizing radiation (IR), ultraviolet (UV) light, and medicines can induce spontaneous DNA lesions [1–3]. However, DNA modifications can also be programmed. In particular, the recombination activating gene (RAG) can induce breaks generated du...
Article
Full-text available
The SARS-CoV-2 proteome shares regions of conservation with endemic human coronaviruses (CoVs), but it remains unknown to what extent these may be cross-recognized by the antibody response. Here, we study cross-reactivity using a highly multiplexed peptide assay (PepSeq) to generate an epitope-resolved view of IgG reactivity across all human CoVs i...
Preprint
Full-text available
There is an urgent need for new antivirals with powerful therapeutic potential and tolerable side effects. In the present study, we found that recombinant human interferon-alpha 2a (IFNa2a) triggers intrinsic and extrinsic cellular antiviral responses, as well as reduces replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in...
Preprint
Full-text available
Therapeutic options for coronavirus remain limited. To address this unmet medical need, we screened 5,406 compounds, including United States Food and Drug Administration (FDA)-approved drugs and bioactives, for activity against a South Korean Middle East respiratory syndrome coronavirus (MERS-CoV) clinical isolate. Among 221 identified hits, 54 had...
Article
Full-text available
Exposure to hepatitis E virus (HEV) bears a high risk of developing chronic infection in immunocompromised patients, including organ transplant recipients and cancer patients. We aim to identify effective anti-HEV therapies through screening and repurposing safe-inhuman broad-spectrum antiviral agents. In this study, a safe-inhuman broad-spectrum a...
Article
Full-text available
Combination therapies have become a standard for the treatment for HIV and hepatitis C virus (HCV) infections. They are advantageous over monotherapies due to better efficacy, reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify new synergistic combination...
Preprint
Full-text available
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...
Preprint
Full-text available
A high-resolution understanding of the antibody response to SARS-CoV-2 is important for the design of effective diagnostics, vaccines and therapeutics. However, SARS-CoV-2 antibody epitopes remain largely uncharacterized, and it is unknown whether and how the response may cross-react with related viruses. Here, we use a multiplexed peptide assay ('...
Article
Full-text available
Background: The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. We hypothesized that not only invasive RNA or DNA (biological factors) but also DNA/RNA-damaging chemical or physical factors could trigger apoptos...
Preprint
Full-text available
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6. 7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus specific v...
Article
Full-text available
As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific va...
Article
Full-text available
Although rotavirus infection is usually acute and self-limiting, it can cause chronic infection with severe diseases in immunocompromised patients, including organ transplantation recipients and cancer patients irrespective of pediatric or adult patients. Since no approved medication against rotavirus infection is available, this study screened a l...
Preprint
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of gene...
Preprint
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of gene...
Article
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of gene...
Research Proposal
Full-text available
2019-nCoV is a novel strain of coronaviruses which is associated with a cluster of cases of pneumonia in China (1). Coronaviruses (CoV) are a broad family of viruses, which include Severe Acute Respiratory Syndrome (SARS)-CoV, Middle East Respiratory Syndrome (MERS)-CoV, human HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 strains. Infections with t...
Preprint
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing th...
Preprint
Full-text available
We demonstrated recently that Bcl-xL-specific inhibitors prematurely killed virus-infected or RNA/DNA-transfected cells. Here we showed that Bcl-xL-specific agent A-1155463 prematurely killed human non-malignant as well as malignant cells and the small roundworm C. elegans when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The s...
Preprint
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing th...
Preprint
Full-text available
Viral diseases are one of the leading causes of morbidity and mortality in the world. Broad-spectrum antiviral agents (BSAAs) are key players in control of human viral diseases. Here, we reviewed the discovery and development process of BSAAs, focusing on compounds with available safety profiles in human. In addition, we summarized the information...
Article
Full-text available
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obato...
Preprint
Full-text available
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obato...
Article
Full-text available
Viruses are one of the major causes of 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...
Article
Broad-spectrum antivirals (BSAs) are agents that inhibit replication of several human viruses. Here, we review 108 approved, investigational, and experimental BSAs, for which safety profiles in humans are available. The most effective and tolerable BSAs could reinforce the arsenal of available antiviral therapeutics pending the results of further p...
Article
Full-text available
With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania dur...
Preprint
Full-text available
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 m...
Article
Full-text available
There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can only be revealed after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory propert...
Article
Full-text available
Here, we report the complete genome sequences of human metapneumovirus (HMPV) prior to and after passaging in LLC-MK2 cells. Paired comparisons of the 13,335-nucleotide genomes revealed that the virus acquired the T10736C transition in its genome, which did not affect the amino acid sequences of HMPV proteins.
Article
Here, we report the complete genome sequences of human metapneumo-virus (HMPV) prior to and after passaging in LLC-MK2 cells. Paired comparisons of the 13,335-nucleotide genomes revealed that the virus acquired the T10736C transition in its genome, which did not affect the amino acid sequences of HMPV proteins.
Article
According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds...
Article
Full-text available
Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or...
Article
Full-text available
Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here...
Preprint
Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here...
Preprint
Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral outbreaks, new treatments are urgently needed. Developing new virus control modalities requires better understanding of virus-host interactions. Here...
Article
Full-text available
An epidemic of Zika virus (ZIKV) infection associated with congenital abnormalities such as microcephaly, is ongoing in the Americas and the Pacific. Currently there are no approved therapies to treat this emerging viral disease. Here, we tested three cell-directed broad-spectrum antiviral compounds against ZIKV replication using human retinal pigm...