Manjesh Saakre1, Deepu Mathew2, V Ravisankar2. 1. National Institute for Plant Biotechnology, Indian Agricultural Research Institute, Pusa, New Delhi, 110 012 India. 2. Bioinformatics Centre, Kerala Agricultural University, Thrissur, 680 656 India.
Abstract
BACKGROUND: The world pandemic COVID-19 caused by SARS-CoV-2 is currently claiming thousands of lives. Flavonoids abundantly present in the fruits and vegetables, especially quercetin, are shown to have antiviral activities. MAIN TEXT: This paper reviews the capability of the plant flavonoid quercetin to fight the novel coronavirus and the possibility for drug development based on this. The mode of action explaining the known pathways through which this molecule succeeds in the antiviral activity, action of quercetin on SARS-CoV-2 main protease 3CLpro, antiviral activities of its derivatives on human viruses, effect of combination of zinc co-factor along with quercetin in the COVID-19 treatment, and the regulation of miRNA genes involved in the viral pathogenesis are discussed. Proof for this concept is provided following the virtual screening using ten key enzymes of SARS-CoV-2 and assessing their interactions. Active residues in the 3D structures have been predicted using CASTp and were docked against quercetin. Key proteins 3CLpro, spike glycoprotein/ human ACE2-BOAT1 complex, RNA-dependent RNA polymerase, main peptidase, spike glycoprotein, RNA replicase, RNA binding protein, papain-like protease, SARS papain-like protease/ deubiquitinase, and complex of main peptidase with an additional Ala at the N-terminus of each protomer, have shown the binding energies ranging between - 6.71 and - 3.37 kcal/ Mol, showing that quercetin is a potential drug candidate inhibiting multiple SARS-CoV-2 enzymes. CONCLUSION: The antiviral properties of flavonoid and the molecular mechanisms involved are reviewed. Further, proof for this concept is given by docking of key proteins from SARS-CoV-2 with quercetin.
BACKGROUND: The world pandemic COVID-19 caused by SARS-CoV-2 is currently claiming thousands of lives. Flavonoids abundantly present in the fruits and vegetables, especially quercetin, are shown to have antiviral activities. MAIN TEXT: This paper reviews the capability of the plant flavonoid quercetin to fight the novel coronavirus and the possibility for drug development based on this. The mode of action explaining the known pathways through which this molecule succeeds in the antiviral activity, action of quercetin on SARS-CoV-2 main protease 3CLpro, antiviral activities of its derivatives on human viruses, effect of combination of zinc co-factor along with quercetin in the COVID-19 treatment, and the regulation of miRNA genes involved in the viral pathogenesis are discussed. Proof for this concept is provided following the virtual screening using ten key enzymes of SARS-CoV-2 and assessing their interactions. Active residues in the 3D structures have been predicted using CASTp and were docked against quercetin. Key proteins 3CLpro, spike glycoprotein/ human ACE2-BOAT1 complex, RNA-dependent RNA polymerase, main peptidase, spike glycoprotein, RNA replicase, RNA binding protein, papain-like protease, SARS papain-like protease/ deubiquitinase, and complex of main peptidase with an additional Ala at the N-terminus of each protomer, have shown the binding energies ranging between - 6.71 and - 3.37 kcal/ Mol, showing that quercetin is a potential drug candidate inhibiting multiple SARS-CoV-2 enzymes. CONCLUSION: The antiviral properties of flavonoid and the molecular mechanisms involved are reviewed. Further, proof for this concept is given by docking of key proteins from SARS-CoV-2 with quercetin.
Authors: Kiira Ratia; Kumar Singh Saikatendu; Bernard D Santarsiero; Naina Barretto; Susan C Baker; Raymond C Stevens; Andrew D Mesecar Journal: Proc Natl Acad Sci U S A Date: 2006-03-31 Impact factor: 11.205
Authors: Aljawharah A Alqathama; Rizwan Ahmad; Ruba B Alsaedi; Raghad A Alghamdi; Ekram H Abkar; Rola H Alrehaly; Ashraf N Abdalla Journal: Pharm Biol Date: 2022-12 Impact factor: 3.503