Periodic Reporting for period 2 - ANTIVIRALS (European Training Network on Antiviral Drug Development)
Período documentado: 2017-03-01 hasta 2019-09-30
Viral infections are a major cause of disease, with enormous costs in morbidity/mortality and economic losses worldwide. Since only a few viral diseases can currently be prevented by vaccination, antiviral therapy is an essential instrument to control virus infections. Antiviral therapies are available for only a few diseases, leading to a great unmet medical need for antiviral drugs to treat or prevent infections with many important human pathogens. In line with this, there is great need for experts in the field which have been trained in a multidisciplinary and intersectoral setting, with attention for both basic and applied aspects of antiviral drug development.
The ANTIVIRALS consortium, consisting of 7 academic and 3 industrial leaders in the field, implemented a research, training and dissemination programme to educate these experts, to advance the field and to create a basis for further use of the results.
The ANTIVIRALS consortium, consisting of 7 academic and 3 industrial leaders in the field, implemented a research, training and dissemination programme to educate these experts, to advance the field and to create a basis for further use of the results.
Training
Fifteen Early Stage Researchers (ESRs) were recruited from around the globe and enrolled in the ANTIVIRALS training programme as well as in local graduate schools. This has led to 13 planned PhD awards in 2019 and 2020. All ESRs participated in both local and network-wide training activities that focussed on both scientific and generic skills and knowledge.
The ANTIVIRALS-organised courses included Virus replication & Evolution, Small-molecule screening, Structural biology & Structure-based drug design, Medicinal Chemistry and Clinical Virology & Antivirals. Apart from these courses, all ESRs performed in the individual secondments and industrial group secondments. An example of an industrial group secondment is the training at Partner Organisation Prestwick Chemicals, where the ESRs searched compounds to build up the Prestwick Fragment Library, which will consist of 2000 fragments that come from already marketed drugs. The ESRs used literature and catalogue searches to come up with proposed fragments for this compound library.
The research training described above was supplemented by complementary skills training in among others management, innovation, communication, dissemination, intellectual property, valorisation, and entrepreneurship. This training was done as workshops, in symposia, during the industrial group secondments and in assignments. The training in generic skills prepared the ESRs for future (research-related) jobs, the jobs that drive Europe’s innovation potential.
A special workshop was the Drug Design and Development Game, led by Prof. Apr. Walter Van Den Broeck (working at Janssen Infectious Diseases), who developed the game based on his 26 years of experience in drug development. For the game, the ESRs formed 4 hypothetical companies (two large pharma companies and two start-up companies). The companies took their compounds through the earlier trajectory of drug development. The management boards of the companies, formed by the ESRs, had to take decisions to put their compound forward. The game gave the ESRs a good feel for the innovation and entrepreneurship and for things that are essential to bring a drug to the market.
Research
The ANTIVIRALS research programme identified and characterised novel inhibitors of replication of a group of medically and socio-economically important viruses. This also gave important insights into the replication mechanisms of these viruses and their interaction with the host cells. The scientific insights were used to improve and design new compounds that could be developed into antiviral drugs based on the inhibitors identified.
An example a highly collaborative project focused on the mode of action of fluoxetine, the active compound of Prozac®, as an inhibitor of enteroviruses, which can cause various diseases ranging from common cold and hand-foot-and-mouth-disease, to serious neurological conditions such as meningitis, encephalitis, and paralysis. By using a combination of computer-aided drug design, medicinal chemistry, virology and structural biology, the ESRs were able to identify a group of compounds based on fluoxetine, that have a broad-spectrum antiviral profile. These results represent a very promising starting point in the development on a new antiviral therapy.
Another project focused on Dengue Virus, which can cause Dengue fever, a painful, debilitating and, in its most severe form, potentially lethal disease. Currently there is not an approved antiviral treatment available. This project was focused on the investigation on how a specific viral protein, NS1, interacts with the host cell and how these interactions affect the virus life cycle. These studies, among other results, have revealed a new role of the NS1 protein in the replication of viral RNA. This discovery could establish the bases of a completely new and innovative strategy in the development of an anti-Dengue therapy.
Dissemination and societal outreach
An important objective of ANTIVIRALS was to disseminate its results to scientists, stakeholders and society. All ESRs were actively involved in public engagements through writing their own blog, face-to-face activities and articles for a wide public. ESRs were trained by one of the best examples of bringing virology to a wider public, Vincent Racanielo (also called “world’s virology professor”), assessed the ESRs’ blog posts and taught them from experiences what’s important in blogging and public engagement. Blogs are still available from http://moodle.phrmy.cf.ac.uk/antivirals_blog/. Each ESR also wrote an item for the broader public, such as other blogs (e.g. https://www.nativescientist.com/single-post/This-is-not-a-bacterium-some-common-misunderstandings-about-viruses) or articles for local newspapers. Importantly, ESRs actively reached out to the broader public by participating in face-to-face events, for example by giving a presentation at their alma mater and contribution to a science festival.
Informing fellow scientists about the scientific results of the project was done in peer-reviewed publications and poster/oral presentations at (inter)national conferences. Already, the project has yielded 25 scientific publications that are openly accessible, with yet more to come. The ESRs all presented their results at conferences and even received prizes for doing so excellently. The ANTIVIRALS final symposium was a satellite meeting of the well-known scientific conference ICAR, and attracted >200 external participants.
Fifteen Early Stage Researchers (ESRs) were recruited from around the globe and enrolled in the ANTIVIRALS training programme as well as in local graduate schools. This has led to 13 planned PhD awards in 2019 and 2020. All ESRs participated in both local and network-wide training activities that focussed on both scientific and generic skills and knowledge.
The ANTIVIRALS-organised courses included Virus replication & Evolution, Small-molecule screening, Structural biology & Structure-based drug design, Medicinal Chemistry and Clinical Virology & Antivirals. Apart from these courses, all ESRs performed in the individual secondments and industrial group secondments. An example of an industrial group secondment is the training at Partner Organisation Prestwick Chemicals, where the ESRs searched compounds to build up the Prestwick Fragment Library, which will consist of 2000 fragments that come from already marketed drugs. The ESRs used literature and catalogue searches to come up with proposed fragments for this compound library.
The research training described above was supplemented by complementary skills training in among others management, innovation, communication, dissemination, intellectual property, valorisation, and entrepreneurship. This training was done as workshops, in symposia, during the industrial group secondments and in assignments. The training in generic skills prepared the ESRs for future (research-related) jobs, the jobs that drive Europe’s innovation potential.
A special workshop was the Drug Design and Development Game, led by Prof. Apr. Walter Van Den Broeck (working at Janssen Infectious Diseases), who developed the game based on his 26 years of experience in drug development. For the game, the ESRs formed 4 hypothetical companies (two large pharma companies and two start-up companies). The companies took their compounds through the earlier trajectory of drug development. The management boards of the companies, formed by the ESRs, had to take decisions to put their compound forward. The game gave the ESRs a good feel for the innovation and entrepreneurship and for things that are essential to bring a drug to the market.
Research
The ANTIVIRALS research programme identified and characterised novel inhibitors of replication of a group of medically and socio-economically important viruses. This also gave important insights into the replication mechanisms of these viruses and their interaction with the host cells. The scientific insights were used to improve and design new compounds that could be developed into antiviral drugs based on the inhibitors identified.
An example a highly collaborative project focused on the mode of action of fluoxetine, the active compound of Prozac®, as an inhibitor of enteroviruses, which can cause various diseases ranging from common cold and hand-foot-and-mouth-disease, to serious neurological conditions such as meningitis, encephalitis, and paralysis. By using a combination of computer-aided drug design, medicinal chemistry, virology and structural biology, the ESRs were able to identify a group of compounds based on fluoxetine, that have a broad-spectrum antiviral profile. These results represent a very promising starting point in the development on a new antiviral therapy.
Another project focused on Dengue Virus, which can cause Dengue fever, a painful, debilitating and, in its most severe form, potentially lethal disease. Currently there is not an approved antiviral treatment available. This project was focused on the investigation on how a specific viral protein, NS1, interacts with the host cell and how these interactions affect the virus life cycle. These studies, among other results, have revealed a new role of the NS1 protein in the replication of viral RNA. This discovery could establish the bases of a completely new and innovative strategy in the development of an anti-Dengue therapy.
Dissemination and societal outreach
An important objective of ANTIVIRALS was to disseminate its results to scientists, stakeholders and society. All ESRs were actively involved in public engagements through writing their own blog, face-to-face activities and articles for a wide public. ESRs were trained by one of the best examples of bringing virology to a wider public, Vincent Racanielo (also called “world’s virology professor”), assessed the ESRs’ blog posts and taught them from experiences what’s important in blogging and public engagement. Blogs are still available from http://moodle.phrmy.cf.ac.uk/antivirals_blog/. Each ESR also wrote an item for the broader public, such as other blogs (e.g. https://www.nativescientist.com/single-post/This-is-not-a-bacterium-some-common-misunderstandings-about-viruses) or articles for local newspapers. Importantly, ESRs actively reached out to the broader public by participating in face-to-face events, for example by giving a presentation at their alma mater and contribution to a science festival.
Informing fellow scientists about the scientific results of the project was done in peer-reviewed publications and poster/oral presentations at (inter)national conferences. Already, the project has yielded 25 scientific publications that are openly accessible, with yet more to come. The ESRs all presented their results at conferences and even received prizes for doing so excellently. The ANTIVIRALS final symposium was a satellite meeting of the well-known scientific conference ICAR, and attracted >200 external participants.
Through the ANTIVIRALS European Training Network, a new generation of researchers was raised, who have a very wide and diverse set of skills. We expect these young researchers will have impact on the future of virology research and the development of antiviral drugs. The broad training programme enables them to have this impact from various branches, such as academic and industrial research as well as science communication and research management. Significant progress has been made in the research programme that will be the basis of further research and possibly of the development of compounds into antiviral drugs. This projects has contributed to a sustainable collaboration between the parties, and thereby contributed to bridging the gap between the academic and the industrial sector.