Thomas Lane1, Manu Anantpadma2,3, Joel S Freundlich4, Robert A Davey2,3, Peter B Madrid5, Sean Ekins6. 1. Collaborations Pharmaceuticals, Inc., Main Campus Drive, Lab 3510 Raleigh, North Carolina, 27606, USA. 2. Texas Biomedical Research Institute, San Antonio, TX, 78227, USA. 3. National Emerging Infectious Diseases Laboratories, Boston University, 401P, 620 Albany Street, Boston, MA, 02118, USA. 4. Departments of Pharmacology & Physiology and Medicine, Center for Emerging and Reemerging Pathogens, Rutgers University - New Jersey Medical School, 185, Avenue Newark, South Orange, NJ, 07103, USA. 5. Biosciences Division, SRI International, 333 Ravenswood Avenue, Menlo Park, California, 94025, USA. 6. Collaborations Pharmaceuticals, Inc., Main Campus Drive, Lab 3510 Raleigh, North Carolina, 27606, USA. sean@collaborationspharma.com.
Abstract
PURPOSE: Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing this manuscript there is an ongoing outbreak in the Democratic Republic of the Congo which has killed over 1000. METHODS: We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. RESULTS: Four compounds possessed EC50 values less than or equal to 11 μM. Of these, eugenol, had an EC50 of 1.3 μM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. CONCLUSION: This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.
PURPOSE: Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing this manuscript there is an ongoing outbreak in the Democratic Republic of the Congo which has killed over 1000. METHODS: We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. RESULTS: Four compounds possessed EC50 values less than or equal to 11 μM. Of these, eugenol, had an EC50 of 1.3 μM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. CONCLUSION: This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.
Entities:
Keywords:
antiviral; drug discovery; ebola; eugenol; p-anisaldehyde
Authors: Louis K S Darko; Emmanuel Broni; Dominic S Y Amuzu; Michael D Wilson; Christian S Parry; Samuel K Kwofie Journal: Biomedicines Date: 2021-11-30