Simplistic perylene-related compounds as inhibitors of tick-borne encephalitis virus reproduction

Nikita A Slesarchuk; Evgeny V Khvatov; Alexey A Chistov; Gleb V Proskurin; Timofei D Nikitin; Anastasiya I Lazarevich; Angelina A Ulanovskaya; Egor A Ulashchik; Alexey A Orlov; Artjom V Jegorov; Alexey V Ustinov; Anton P Tyurin; Vadim V Shmanai; Aydar A Ishmukhametov; Vladimir A Korshun; Dmitry I Osolodkin; Liubov I Kozlovskaya; Andrey V Aralov

doi:10.1016/j.bmcl.2020.127100

Simplistic perylene-related compounds as inhibitors of tick-borne encephalitis virus reproduction

Bioorg Med Chem Lett. 2020 May 15;30(10):127100. doi: 10.1016/j.bmcl.2020.127100. Epub 2020 Mar 9.

Authors

Nikita A Slesarchuk¹, Evgeny V Khvatov², Alexey A Chistov³, Gleb V Proskurin⁴, Timofei D Nikitin⁵, Anastasiya I Lazarevich⁶, Angelina A Ulanovskaya⁶, Egor A Ulashchik⁷, Alexey A Orlov⁸, Artjom V Jegorov⁴, Alexey V Ustinov⁹, Anton P Tyurin¹⁰, Vadim V Shmanai⁷, Aydar A Ishmukhametov¹¹, Vladimir A Korshun¹⁰, Dmitry I Osolodkin¹², Liubov I Kozlovskaya¹¹, Andrey V Aralov⁴

Affiliations

¹ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia; Department of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117312, Russia.
² Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; FSBSI «Chumakov FSC R&D IBP RAS», Moscow 108819, Russia.
³ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117312, Russia.
⁴ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia.
⁵ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia.
⁶ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Mendeleev University of Chemical Technology, Moscow 125047, Russia.
⁷ Institute of Physico-Organic Chemistry, Minsk 220072, Belarus.
⁸ FSBSI «Chumakov FSC R&D IBP RAS», Moscow 108819, Russia.
⁹ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117312, Russia. Electronic address: austinov@yandex.ru.
¹⁰ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117312, Russia; Gause Institute of New Antibiotics, Moscow 119021, Russia.
¹¹ FSBSI «Chumakov FSC R&D IBP RAS», Moscow 108819, Russia; Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow 119991, Russia.
¹² Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia; FSBSI «Chumakov FSC R&D IBP RAS», Moscow 108819, Russia; Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Moscow 119991, Russia. Electronic address: osolodkin_di@chumakovs.su.

PMID: 32199731
DOI: 10.1016/j.bmcl.2020.127100

Abstract

Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophilic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxylic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM.

Keywords: Antiviral activity; Antivirals; Heliomycin; RAFI; Tick-borne encephalitis virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Line
Cell Survival / drug effects
Encephalitis Viruses, Tick-Borne / drug effects*
Encephalitis Viruses, Tick-Borne / physiology
Perylene / chemistry*
Perylene / pharmacology
Structure-Activity Relationship
Swine
Ticks / virology*
Virus Replication / drug effects

Substances

Antiviral Agents
Perylene