Persicamidines-Unprecedented Sesquarterpenoids with Potent Antiviral Bioactivity against Coronaviruses

Lena Keller; Emilia Oueis; Amninder Kaur; Nasim Safaei; Susanne H Kirsch; Antonia P Gunesch; Sibylle Haid; Ulfert Rand; Luka Čičin-Šain; Chengzhang Fu; Joachim Wink; Thomas Pietschmann; Rolf Müller

doi:10.1002/anie.202214595

Persicamidines-Unprecedented Sesquarterpenoids with Potent Antiviral Bioactivity against Coronaviruses

Angew Chem Int Ed Engl. 2023 Feb 1;62(6):e202214595. doi: 10.1002/anie.202214595. Epub 2023 Jan 4.

Authors

Lena Keller^{1

2}, Emilia Oueis^{1

3}, Amninder Kaur^{1

4}, Nasim Safaei^{4

5

6}, Susanne H Kirsch^{1

4}, Antonia P Gunesch^{4

6}, Sibylle Haid^{4

6}, Ulfert Rand^{4

6}, Luka Čičin-Šain^{4

6}, Chengzhang Fu^{1

4}, Joachim Wink^{4

5}, Thomas Pietschmann^{4

6}, Rolf Müller^{1

4

7}

Affiliations

¹ Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University Campus, 66123, Saarbrücken, Germany.
² Weincampus Neustadt, Department of Applied Logistics and Polymer Sciences, University of Applied Science Kaiserslautern, Carl-Schurz-Straße 10-16, 66953, Pirmasens, Germany.
³ Department of Chemistry, Khalifa University, PO Box 127788, Abu Dhabi, United Arab Emirates.
⁴ German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124, Braunschweig, Germany.
⁵ Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany.
⁶ TWINCORE Centre for Experimental and Clinical Infection Research GmbH, Institute for Experimental Virology, Feodor-Lynen-Str. 7, 30625, Hannover, Germany.
⁷ Department of Pharmacy, Saarland University, 66123, Saarbrücken, Germany.

Abstract

A new family of highly unusual sesquarterpenoids (persicamidines A-E) exhibiting significant antiviral activity was isolated from a newly discovered actinobacterial strain, Kibdelosporangium persicum sp. nov., collected from a hot desert in Iran. Extensive NMR analysis unraveled a hexacyclic terpenoid molecule with a modified sugar moiety on one side and a highly unusual isourea moiety fused to the terpenoid structure. The structures of the five analogues differed only in the aminoalkyl side chain attached to the isourea moiety. Persicamidines A-E showed potent activity against hCoV-229E and SARS-CoV-2 viruses in the nanomolar range together with very good selectivity indices, making persicamidines promising as starting points for drug development.

Keywords: Actinobacteria; Antiviral Agents; Oleandrose; Sesquarterpenes; Structure Elucidation.

Publication types

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

MeSH terms

Antiviral Agents / chemistry
COVID-19*
Coronavirus 229E, Human*
Humans
Plant Extracts
SARS-CoV-2

Substances

Antiviral Agents
Plant Extracts