Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.

Houttuynia cordata Thunb., a perennial herb belonging to the Saururaceae family is a well-known ingredient of Traditional Chinese medicine (TCM) with several therapeutic properties. During the severe acute respiratory syndrome (SARS) outbreak in China, it was one of the approved ingredients in SARS...

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Autores principales:	Arun Bahadur Gurung, Mohammad Ajmal Ali, Joongku Lee, Mohammad Abul Farah, Khalid Mashay Al-Anazi, Fahad Al-Hemaid
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Coronaviruses Coronaviral RdRp Houttuynia cordata Bioactive compounds Natural products COVID-19 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/665c9cebb99f40a990cb391db9874390
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spelling	oai:doaj.org-article:665c9cebb99f40a990cb391db98743902021-11-20T04:57:17ZIdentification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.1319-562X10.1016/j.sjbs.2021.08.100https://doaj.org/article/665c9cebb99f40a990cb391db98743902021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1319562X21007889https://doaj.org/toc/1319-562XHouttuynia cordata Thunb., a perennial herb belonging to the Saururaceae family is a well-known ingredient of Traditional Chinese medicine (TCM) with several therapeutic properties. During the severe acute respiratory syndrome (SARS) outbreak in China, it was one of the approved ingredients in SARS preventative formulations and therefore, the plant may contain novel bioactive chemicals that can be used to suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus for which there are currently no effective drugs available. Like all RNA viruses, SARS-CoV-2 encode RNA-dependent RNA polymerase (RdRp) enzyme which aids viral gene transcription and replication. The present study is aimed at understanding the potential of bioactive compounds from H. cordata as inhibitors of the SARS-CoV-2 RdRp enzyme. We investigated the drug-likeness of the plant's active constituents, such as alkaloids, polyphenols, and flavonoids, as well as their binding affinity for the RdRp enzyme. Molecular docking experiments show that compounds 3 (1,2,3,4,5-pentamethoxy-dibenzo-quinolin-7-one), 14 (7-oxodehydroasimilobine), and 21 (1,2-dimethoxy-3-hydroxy-5-oxonoraporphine) have a high affinity for the drug target and that the complexes are maintained by hydrogen bonds with residues like Arg553, Cys622 and Asp623, as well as hydrophobic interactions with other residues. The lead compounds' complexes with the target enzyme remained stable throughout the molecular dynamics simulation. Analysis of molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA) revealed the key residues contributing considerably to binding free energy. Thus, the findings reveal the potential of H. cordata bioactive compounds as anti-SARS-CoV-2 drug candidate molecules against the target enzyme.Arun Bahadur GurungMohammad Ajmal AliJoongku LeeMohammad Abul FarahKhalid Mashay Al-AnaziFahad Al-HemaidElsevierarticleCoronavirusesCoronaviral RdRpHouttuynia cordataBioactive compoundsNatural productsCOVID-19Biology (General)QH301-705.5ENSaudi Journal of Biological Sciences, Vol 28, Iss 12, Pp 7517-7527 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Coronaviruses Coronaviral RdRp Houttuynia cordata Bioactive compounds Natural products COVID-19 Biology (General) QH301-705.5
spellingShingle	Coronaviruses Coronaviral RdRp Houttuynia cordata Bioactive compounds Natural products COVID-19 Biology (General) QH301-705.5 Arun Bahadur Gurung Mohammad Ajmal Ali Joongku Lee Mohammad Abul Farah Khalid Mashay Al-Anazi Fahad Al-Hemaid Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
description	Houttuynia cordata Thunb., a perennial herb belonging to the Saururaceae family is a well-known ingredient of Traditional Chinese medicine (TCM) with several therapeutic properties. During the severe acute respiratory syndrome (SARS) outbreak in China, it was one of the approved ingredients in SARS preventative formulations and therefore, the plant may contain novel bioactive chemicals that can be used to suppress the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus for which there are currently no effective drugs available. Like all RNA viruses, SARS-CoV-2 encode RNA-dependent RNA polymerase (RdRp) enzyme which aids viral gene transcription and replication. The present study is aimed at understanding the potential of bioactive compounds from H. cordata as inhibitors of the SARS-CoV-2 RdRp enzyme. We investigated the drug-likeness of the plant's active constituents, such as alkaloids, polyphenols, and flavonoids, as well as their binding affinity for the RdRp enzyme. Molecular docking experiments show that compounds 3 (1,2,3,4,5-pentamethoxy-dibenzo-quinolin-7-one), 14 (7-oxodehydroasimilobine), and 21 (1,2-dimethoxy-3-hydroxy-5-oxonoraporphine) have a high affinity for the drug target and that the complexes are maintained by hydrogen bonds with residues like Arg553, Cys622 and Asp623, as well as hydrophobic interactions with other residues. The lead compounds' complexes with the target enzyme remained stable throughout the molecular dynamics simulation. Analysis of molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA) revealed the key residues contributing considerably to binding free energy. Thus, the findings reveal the potential of H. cordata bioactive compounds as anti-SARS-CoV-2 drug candidate molecules against the target enzyme.
format	article
author	Arun Bahadur Gurung Mohammad Ajmal Ali Joongku Lee Mohammad Abul Farah Khalid Mashay Al-Anazi Fahad Al-Hemaid
author_facet	Arun Bahadur Gurung Mohammad Ajmal Ali Joongku Lee Mohammad Abul Farah Khalid Mashay Al-Anazi Fahad Al-Hemaid
author_sort	Arun Bahadur Gurung
title	Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
title_short	Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
title_full	Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
title_fullStr	Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
title_full_unstemmed	Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.
title_sort	identification of sars-cov-2 inhibitors from extracts of houttuynia cordata thunb.
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/665c9cebb99f40a990cb391db9874390
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Identification of SARS-CoV-2 inhibitors from extracts of Houttuynia cordata Thunb.

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