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. 2023 Jun;31(1):51-68.
doi: 10.1007/s40199-023-00461-3. Epub 2023 May 17.

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies

Larissa Toigo  1 , Emilly Isabelli Dos Santos Teodoro  2 , Ana Carolina Guidi  2 , Naiara Cássia Gancedo  2 , Marcus Vinícius Petruco  3 , Eduardo Borges Melo  1 , Fernanda Stumpf Tonin  4   5 , Fernando Fernandez-Llimos  6 , Danielly Chierrito  1   7 , João Carlos Palazzo de Mello  2 , Daniela Cristina de Medeiros Araújo  7 , Andréia Cristina Conegero Sanches  8
Affiliations

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies

Larissa Toigo et al. Daru. 2023 Jun.

Erratum in

Abstract

Objectives: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process.

Methods: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection.

Results: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside.

Conclusion: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.

Keywords: Coronavirus; Flavonoids; In silico; Respiratory Syndrome.

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Conflict of interest statement

The authors declare that there is no conflict of interest in relation to the data presented in this publication.

Figures

Fig. 1
Fig. 1
Flowchart of the study selection process
Fig. 2
Fig. 2
Chemical structures described in the most promising results of the 37 in silico studies drawn by ChemDraw version 14.0.0.118. The chemical structures of flavonoids mentioned, correspond to: (1) orientin; (2) quercetin; (3) epigallocatechin; (4) narcissoside; (5) silymarin; (6) neohesperidin; (7) delphinidin-3,5-diglucoside; (8) delphinidin-3-sambubioside-5-glucoside; (9) amentoflavone; (10) baicalein; (11) biochanin A; (12) calophyllolide; (13) cyanidin; (14) cyanidin-3-glucoside; (15) cyaniding-3-rutinoside; (16) eriodictyol; (17) fisetin; (18) hesperidin; (19) hesperitin; (20) kaempferol; (21) luteolin; (22) naringin; (23) pectolinarin; (24) rhamnetin; (25) rhoifolin; (26) rutin; (27) theaflavin; (28) theaflavin-3,3’- digallate; (29) theaflavin monogallate
Fig. 2
Fig. 2
Chemical structures described in the most promising results of the 37 in silico studies drawn by ChemDraw version 14.0.0.118. The chemical structures of flavonoids mentioned, correspond to: (1) orientin; (2) quercetin; (3) epigallocatechin; (4) narcissoside; (5) silymarin; (6) neohesperidin; (7) delphinidin-3,5-diglucoside; (8) delphinidin-3-sambubioside-5-glucoside; (9) amentoflavone; (10) baicalein; (11) biochanin A; (12) calophyllolide; (13) cyanidin; (14) cyanidin-3-glucoside; (15) cyaniding-3-rutinoside; (16) eriodictyol; (17) fisetin; (18) hesperidin; (19) hesperitin; (20) kaempferol; (21) luteolin; (22) naringin; (23) pectolinarin; (24) rhamnetin; (25) rhoifolin; (26) rutin; (27) theaflavin; (28) theaflavin-3,3’- digallate; (29) theaflavin monogallate
Fig. 3
Fig. 3
SARS-CoV-2 life cycle in the main flavonoids discuss in the scoping review. 1. Shows the main structural and non-structural target proteins of SARS-CoV-2 discussed in the review. The most promising flavonoids analyzed in silico study for (A) protein S were quercetin, eriodictyol, hesperidin, calophyllolide, fisetin, orientin, luteolin, and biochanin A; (B) ORF 1a (PLpro) were quercetin, eriodictyol, hesperidin, and luteolin; (B) ORF 1a (Mpro) were rutin, kaempferol, delphinidin-3-sambubioside-5-glucoside, quercetin, eriodictyol, calophyllolide, delphinidin-3,5-diglucoside, orientin, rhamnetin, and cyanidin-3-glucoside; (B) ORF 1a (3CLpro) were amentoflavone, quercetin, hesperidin, naringin, pectolinarin, cyanidin-3-rutinoside, baicalein, luteolin, rhoifolin, and narcissoside; (C) ORF 1b (RdRP) were quercetin, epigallocatechin, calophyllolide, theaflavin-3,3’-digallate, luteolin, and theaflavin. In 2, the main cellular targets discussed in this study are shown, being (D) ACE 2 and (E) TMPRSS2, and the flavonoids observed for these targets were for (D) quercetin, cyanidin, theaflavin monogallate, delphinidin-3,5-diglucoside, orientin, and silymarin/Silibinin (silybin A); and for (E) neohesperidin, hesperidin
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