Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies


Posted: 2021-09-27 19:00:00
Results Chem . 2021 Jan;3:100195. doi: 10.1016/j.rechem.2021.100195. Epub 2021 Sep 20. Affiliations Expand Affiliations 1 Faculty of Pharmacy, Sanata Dharma University, Campus III, Paingan, Maguwoharjo, Depok, Sleman 55282, Yogyakarta, Indonesia. 2 Chemistry Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang 45363, West Java, Indonesia. 3 Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institute of Biotechnology Malaysia, Halaman Bukit Gambir, 11900 Bayan Lepas, Pulau Pinang, Malaysia. 4 Pharmaceutical Technology Department, School of Pharmaceutical Sciences and USM-RIKEN Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Item in Clipboard Maywan Hariono et al. Results Chem. 2021 Jan. Show details Display options Display options Format Results Chem . 2021 Jan;3:100195. doi: 10.1016/j.rechem.2021.100195. Epub 2021 Sep 20. Affiliations 1 Faculty of Pharmacy, Sanata Dharma University, Campus III, Paingan, Maguwoharjo, Depok, Sleman 55282, Yogyakarta, Indonesia. 2 Chemistry Department, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jatinangor, Sumedang 45363, West Java, Indonesia. 3 Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institute of Biotechnology Malaysia, Halaman Bukit Gambir, 11900 Bayan Lepas, Pulau Pinang, Malaysia. 4 Pharmaceutical Technology Department, School of Pharmaceutical Sciences and USM-RIKEN Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800 Minden, Pulau Pinang, Malaysia. Item in Clipboard CiteDisplay options Display options Format Abstract This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e., Averrhoa carambola leaves and Ageratum conyzoides aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The in vitro results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the in vitro activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC-MS) analysis reported chromene compounds in Ageratum conyzoides aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism. Keywords: 3CLpro; Chromene; Docking; Flavonoid; Hydroxamic acid; In vitro; Pharmacophore; SARS-CoV-2. © 2021 The Authors. Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

参考サイト PubMed: covid-19


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バイオクイックニュース日本語版:COVID-19特集

バイオクイックニュース日本語版
4月 07, 2020 バイオアソシエイツ

米国の2人の感染症専門家がCOVID-19生存者からの抗体を、患者治療と医療従事者保護の応急措置として使用すべきと主張。 このアプローチは100年間に渡り致命的な病原体の大発生で成功を収めている。

新型コロナウイルス( COVID-19 )と闘う国々は、感染から回復した人々の抗体を使用して症例を治療し、重要な医療従事者に短期免疫(数週間から数ヶ月)を提供することを検討する必要があると米国の2人の感染症専門家が主張している。 ボルティモアにあるジョンズホプキンスブルームバーグ公衆衛生学校の分子微生物学および免疫学科の部長であるArturo Casadevall医学博士とニューヨーク市にあるアルバートアインシュタイン医科大学の感染症部門の責任者であるLiise-anne Pirofski医学博士である。…

ゲスト 488人 と メンバー 2人 がオンラインです