Mono- and combinational drug therapies for global viral pandemic preparedness
Aleksandr Ianevski,
Rouan Yao,
Ronja M. Simonsen,
Vegard Myhre,
Erlend Ravlo,
Gerda D. Kaynova,
Eva Zusinaite,
Judith M. White,
Stephen J. Polyak,
Valentyn Oksenych,
Marc P. Windisch,
Qiuwei Pan,
Eglė Lastauskienė,
Astra Vitkauskienė,
Algimantas Matukevičius,
Tanel Tenson,
Magnar Bjørås,
Denis E. Kainov
Affiliations
Aleksandr Ianevski
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Rouan Yao
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Ronja M. Simonsen
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Vegard Myhre
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Erlend Ravlo
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Gerda D. Kaynova
Vilnius Ozo Gymnasium, Vilnius University, Vilnius 07171, Lithuania
Eva Zusinaite
Institute of Technology, University of Tartu, 50411 Tartu, Estonia
Judith M. White
University of Virginia, Department of Cell Biology, Charlottesville, VA, USA
Stephen J. Polyak
Virology Division, Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
Valentyn Oksenych
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Marc P. Windisch
Applied Molecular Virology Laboratory, Institut Pasteur Korea, 463-400 Gyeonggi-do, Korea
Qiuwei Pan
Department of Gastroenterology and Hepatology, Erasmus MC-University, Medical Center, Rotterdam, Netherlands
Eglė Lastauskienė
Life Sciences Center, Vilnius University, 10257 Vilnius, Lithuania
Astra Vitkauskienė
Department of Laboratory Medicine, Lithuanian University of Health Science, 44307 Kaunas, Lithuania
Algimantas Matukevičius
Department of Laboratory Medicine, Lithuanian University of Health Science, 44307 Kaunas, Lithuania
Tanel Tenson
Institute of Technology, University of Tartu, 50411 Tartu, Estonia
Magnar Bjørås
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway
Denis E. Kainov
Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology (NTNU), 7028 Trondheim, Norway; Institute of Technology, University of Tartu, 50411 Tartu, Estonia; Institute for Molecular Medicine Finland, University of Helsinki, 00014 Helsinki, Finland; Corresponding author
Summary: 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, immunomodulatory properties of available broad-spectrum antivirals (BSAs), routes of BSA delivery, and interactions of BSAs with other antivirals. Based on the review, we concluded that the range of indications of BSAs can be expanded, and new pan- and cross-viral mono- and combinational therapies can be developed. We have also developed a new scoring algorithm that can help identify the most promising few of the thousands of potential BSAs and BSA-containing drug cocktails (BCCs) to prioritize their development during the critical period between the identification of a new virus and the development of virus-specific vaccines, drugs, and therapeutic antibodies.
