Potential antiviral activity of isorhamnetin against SARS‐CoV‐2 spike pseudotyped virus in vitro

Abstract

Coronavirus Disease 2019 (COVID-19) cases and deaths are still rising worldwide, there is currently no effective treatment for severe inflammation and acute lung injury caused by new coronavirus (SARS-COV-2) infection. Therapies to prevent or treat COVID-19, including antiviral drug and several vaccines, are still being development. Human angiotensin-converting enzyme 2 (ACE2), expressing in lung, has been confirmed to be a receptor for SARS-COV-2 infection, interventions for attachment of spike protein of SARS-CoV-2 to ACE2 may be a potential approach to prevent viral infections and it is considered as a potential target for drug development. In this study, we observed that seabuckthorn and its flavonoid compounds quercetin and isorhamnetin were shown strong retention to ACE2 overexpression HEK293 (ACE2 h ) cells by CMC analysis. Based on drug receptor interaction analysis and viral entry studies in vitro, we evaluated the interaction of two flavonoid compounds and ACE2 as well as the inhibitory effect of the two compounds on viral entry. Surface plasmon resonance assay proved the effect that isorhamnetin bound to the ACE2, and its affinity (KD value) was at the micromolar level, that was, 2.51 ± 0.68 μM. Viral entry studies in vitro indicated that isorhamnetin inhibited SARS-CoV-2 spike pseudotyped virus entering ACE2 h cells. Based on promising in vitro results, we proposed isorhamnetin to be a potential therapeutic candidate compound against COVID-19.

Sea Buckthorn Leaf Powders: The Impact of Cultivar and Drying Mode on Antioxidant, Phytochemical, and Chromatic Profile of Valuable Resource

“…Chemophenetically isorhamnetin glycosides prevail over quercetin glycosides [ 19 ]. Recent findings on the isorhamnetin’s capability to bind to human angiotensin-converting enzyme 2 and prevent the SARS-CoV-2 virus from entering the cells [ 13 ] could initiate further research on the valorization of HR leaves for the production of isorhamnetin. The leaf powders of ‘Otradnaja’ and ‘Podarok Sadu’ were determined with the greatest amounts of kaempferol derivatives.…”

“…The traditional medicinal systems incorporate the fruits and leaves of HR in the treatment of various ailments of digestive, hepatic, and cardiovascular systems, as well as skin diseases [ 3 , 4 ]. In vitro and in vivo studies have confirmed the anti-inflammatory, antitumor, hepatoprotective, immunomodulatory, anti-atherogenic, anti-stress, hepatoprotective, radioprotective, tissue repair, antibacterial, antifungal, antiviral, and antioxidant activities, which are determined by the multichemical origin compounds [ 4 , 9 , 10 , 11 , 12 , 13 ]. Fruits and leaves contain rich profiles of carotenoids, tocopherols, amino acids, triterpenic compounds, and phenolic compounds [ 3 , 5 , 7 , 8 , 10 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ].…”

“…The leaves contain similar phytochemical profiles as fruits, but have significantly higher amounts of phenolic compounds, especially hydrolysable and condensed tannins, triterpenic compounds, and flavonoids [ 10 , 19 , 20 , 21 ]. Flavonol isorhamnetin, in the frame of the COVID-19 pandemic situation, gained scientific attention, due to its capabilities of in vitro inhibition on the entrance of SARS-CoV-2 spike pseudo-typed virus into cells [ 13 ]. Results suggest great potential for isorhamnetin-rich materials of HR as candidates in COVID-19 management.…”

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review

“…Liu et al (2021) found that baicalein could inhibit SARS-CoV-2 3CLpro activity in vitro with IC50 values of 8.52 µg/ml and 0.39 µM. The effect of isorhamnetin binding to ACE2 was demonstrated by the surface plasmon resonance assay, and it was shown by in vitro virus experiments that isorhamnetin could inhibit SARS-CoV-2 spike pseudotyped virus entering ACE2h cells (Zhan et al, 2021). Antiinflammatory and antiviral effects of stigmasterol and β-sitosterol were demonstrated in in vitro experimental studies (Petrera et al, 2014;Liao et al, 2018).…”

Therapeutic Effects and Molecular Mechanisms of Bioactive Compounds Against Respiratory Diseases: Traditional Chinese Medicine Theory and High-Frequency Use

“…Lindl., and Ginkgo biloba L., and isorhamnetin found in Lepidium apetalum Willd., Eriobotrya japonica (Thunb.) Lindl., Ginkgo biloba L., and Aster tataricus L.f. exhibit the ability to prevent SARS-CoV-2 from entering into ACE2 + cells (Henss et al, 2021;Maiti and Banerjee, 2021;Zhan et al, 2021). Neochlorogenic acid from Tussilago farfara L. and Lianhuaqingwen granules inhibit the ACE2 enzyme activity (Chen et al, 2021a).…”