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Mini-Review Article

Identification of Flavonoids as Potent Inhibitors Against MERS-CoV 3C-like Protease

Author(s): Fatemeh Abdi and Shahrzad Javanshir*

Volume 3, Issue 1, 2022

Published on: 09 July, 2021

Article ID: e221221194665 Pages: 9

DOI: 10.2174/2666796702666210709115659

Price: $65

Abstract

In 2012, a coronavirus was isolated from a patient with severe pneumonia. This betacoronavirus, which appeared in Saudi Arabia, was named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). MERS-CoV is the sixth identified coronavirus that has the ability to infect humans. The Middle East respiratory syndrome-coronavirus (MERS-CoV) is a zoonotic pathogen transmitted between animals and humans. To date, MERS-CoV is responsible for an epidemic that is still ongoing, but limited to the Arabian Peninsula, with a total number of more than 2000 cases identified and a mortality rate of around 35%. The largest outbreaks of human-to-human transmission were reported in Jeddah in 2014 and South Korea in 2015. This infection causes a high mortality rate and no vaccine or medical countermeasures are currently available. Currently, no specific treatment or vaccine is available against this virus. The current challenge is to contain the epidemic and continue research efforts to develop a vaccine and a treatment. Certain flavonoids inhibit the replication of viral RNA and have therapeutic potential against viruses and bacteria. Therefore, it is suggested that flavonoids with these characteristics can be used as models to develop potent inhibitors of MERS-CoV. This work reviews current knowledge and provides an update on MERS-CoV and MERS-CoV 3Clpro virology, epidemiology, clinical features, and the use of flavonoids as potential inhibitors and therapeutic agents for MERS-CoV, and MERS-CoV 3Clpro. This review tries to elucidate the structure-activity relationships (SAR) of varied polyphenols against MERS-CoV 3C-like protease (3Clpro).

Keywords: MERS-CoV, MERS-CoV 3Clpro, flavonoid, inhibitory effect, antiviral activity, structure-activity relationships (SAR).

Graphical Abstract

[1]
Thompson RN, Stockwin JE, van Gaalen RD, et al. Improved inference of time-varying reproduction numbers during infectious disease outbreaks. Epidemics 2019; 29: 100356.
[http://dx.doi.org/10.1016/j.epidem.2019.100356] [PMID: 31624039]
[2]
Jones KE, Patel NG, Levy MA, et al. Global trends in emerging infectious diseases. Nature 2008; 451(7181): 990-3.
[http://dx.doi.org/10.1038/nature06536] [PMID: 18288193]
[3]
Dighe A, Jombart T, Van Kerkhove MD, Ferguson N. A systematic review of MERS-CoV seroprevalence and RNA prevalence in dromedary camels: Implications for animal vaccination. Epidemics 2019; 29: 100350.
[http://dx.doi.org/10.1016/j.epidem.2019.100350] [PMID: 31201040]
[4]
Fehr AR, Perlman S. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol Biol 2015; 1282: 1-23.
[http://dx.doi.org/10.1007/978-1-4939-2438-7_1] [PMID: 25720466]
[5]
Al Ghamdi M, Alghamdi KM, Ghandoora Y, et al. Treatment outcomes for patients with middle eastern respiratory syndrome coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis 2016; 16(1): 174.
[http://dx.doi.org/10.1186/s12879-016-1492-4] [PMID: 27097824]
[6]
Baharoon S, Memish ZA. MERS-CoV as an emerging respiratory illness: A review of prevention methods. Travel Med Infect Dis 2019; 32: 101520.
[http://dx.doi.org/10.1016/j.tmaid.2019.101520] [PMID: 31730910]
[7]
Dhama K, Patel SK, Sharun K, et al. SARS-CoV-2 jumping the species barrier: Zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus. Travel Med Infect Dis 2020; 37: 101830.
[http://dx.doi.org/10.1016/j.tmaid.2020.101830] [PMID: 32755673]
[8]
Mesel-Lemoine M, Millet J, Vidalain PO, et al. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes. J Virol 2012; 86(14): 7577-87.
[http://dx.doi.org/10.1128/JVI.00269-12] [PMID: 22553325]
[9]
Jo S, Kim H, Kim S, Shin DH, Kim MS. Characteristics of flavonoids as potent MERS-CoV 3C-like protease inhibitors. Chem Biol Drug Des 2019; 94(6): 2023-30.
[http://dx.doi.org/10.1111/cbdd.13604] [PMID: 31436895]
[10]
Woo PC, Lau SK, Lam CS, et al. Discovery of seven novel Mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 2012; 86(7): 3995-4008.
[http://dx.doi.org/10.1128/JVI.06540-11] [PMID: 22278237]
[11]
Abolfotouh MA, AlQarni AA, Al-Ghamdi SM, Salam M, Al-Assiri MH, Balkhy HH. An assessment of the level of concern among hospital-based health-care workers regarding MERS outbreaks in Saudi Arabia. BMC Infect Dis 2017; 17(1): 4.
[http://dx.doi.org/10.1186/s12879-016-2096-8] [PMID: 28049440]
[12]
Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367(19): 1814-20.
[http://dx.doi.org/10.1056/NEJMoa1211721] [PMID: 23075143]
[13]
Madani TA, Azhar EI, Hashem AM. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med 2014; 371(14): 1360.
[PMID: 25271614]
[14]
El-Kafrawy SA, Corman VM, Tolah AM, et al. Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: A prospective genomic study. Lancet Planet Health 2019; 3(12): e521-8.
[http://dx.doi.org/10.1016/S2542-5196(19)30243-8] [PMID: 31843456]
[15]
Kim KH, Tandi TE, Choi JW, Moon JM, Kim MS. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: Epidemiology, characteristics and public health implications. J Hosp Infect 2017; 95(2): 207-13.
[http://dx.doi.org/10.1016/j.jhin.2016.10.008] [PMID: 28153558]
[16]
Oh MD, Park WB, Park SW, et al. Middle East respiratory syndrome: What we learned from the 2015 outbreak in the Republic of Korea. Korean J Intern Med (Korean Assoc Intern Med) 2018; 33(2): 233-46.
[http://dx.doi.org/10.3904/kjim.2018.031] [PMID: 29506344]
[17]
Kilianski A, Mielech A, Deng X, Baker SC. Assessing activity and inhibition of MERS-CoV papain-like and 3C-like proteases using luciferase-based biosensors. J Virol 2013; 1-31.
[http://dx.doi.org/10.1128/JVI.02105-13] [PMID: 23986593]
[18]
Kandeel M, Altaher A. Synonymous and biased codon usage by MERS CoV papain-like and 3CL-proteases. Biol Pharm Bull 2017; 40(7): 1086-91.
[http://dx.doi.org/10.1248/bpb.b17-00168] [PMID: 28420819]
[19]
Needle D, Lountos GT, Waugh DS. Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity. Acta Crystallogr D Biol Crystallogr 2015; 71(Pt 5): 1102-11.
[http://dx.doi.org/10.1107/S1399004715003521] [PMID: 25945576]
[20]
Li SY, Chen C, Zhang HQ, et al. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res 2005; 67(1): 18-23.
[http://dx.doi.org/10.1016/j.antiviral.2005.02.007] [PMID: 15885816]
[21]
Lin CW, Tsai FJ, Tsai CH, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res 2005; 68(1): 36-42.
[http://dx.doi.org/10.1016/j.antiviral.2005.07.002] [PMID: 16115693]
[22]
Ghildiyal R, Prakash V, Chaudhary VK, Gupta V, Gabrani R. Phytochemicals as antiviral agents: Recent updates. Plant-derived bioactives. 2020; pp. 279-95.
[23]
Yonekura-Sakakibara K, Higashi Y, Nakabayashi R. The origin and evolution of plant flavonoid metabolism. Front Plant Sci 2019; 10: 943.
[http://dx.doi.org/10.3389/fpls.2019.00943] [PMID: 31428108]
[24]
Hayat M, Abbas M, Munir F, Hayat MQ, Keyani R, Amir R. Potential of plant flavonoids in pharmaceutics and nutraceutics. J Biomolec Biochem 2017; 1(1): 12-7.
[25]
Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000; 52(4): 673-751.
[PMID: 11121513]
[26]
Gorlach S, Fichna J, Lewandowska U. Polyphenols as mitochondria-targeted anticancer drugs. Cancer Lett 2015; 366(2): 141-9.
[http://dx.doi.org/10.1016/j.canlet.2015.07.004] [PMID: 26185003]
[27]
Iranshahi M, Rezaee R, Parhiz H, Roohbakhsh A, Soltani F. Protective effects of flavonoids against microbes and toxins: The cases of hesperidin and hesperetin. Life Sci 2015; 137: 125-32.
[http://dx.doi.org/10.1016/j.lfs.2015.07.014] [PMID: 26188593]
[28]
Khan N, Syed D N, Ahmad N, Mukhtar H. Fisetin: A dietary antioxidant for health promotion. Antioxidants & redox signaling 2013; 19(2): 151-62.
[http://dx.doi.org/10.1089/ars.2012.4901]
[29]
Nabavi SF, Braidy N, Habtemariam S, et al. Neuroprotective effects of chrysin: From chemistry to medicine. Neurochem Int 2015; 90: 224-31.
[http://dx.doi.org/10.1016/j.neuint.2015.09.006] [PMID: 26386393]
[30]
Xia EQ, Deng GF, Guo YJ, Li HB. Biological activities of polyphenols from grapes. Int J Mol Sci 2010; 11(2): 622-46.
[http://dx.doi.org/10.3390/ijms11020622] [PMID: 20386657]
[31]
Yang Y, Zhang L, Geng H, et al. The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 2013; 4(12): 951-61.
[http://dx.doi.org/10.1007/s13238-013-3096-8] [PMID: 24318862]
[32]
Fehr AR, Channappanavar R, Perlman S. Middle East respiratory syndrome: Emergence of a pathogenic human coronavirus. Annu Rev Med 2017; 68: 387-99.
[http://dx.doi.org/10.1146/annurev-med-051215-031152] [PMID: 27576010]
[33]
Memish ZA, Perlman S, Van Kerkhove MD, Zumla A. Middle East respiratory syndrome. Lancet 2020; 395(10229): 1063-77.
[http://dx.doi.org/10.1016/S0140-6736(19)33221-0] [PMID: 32145185]
[34]
Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013; 495(7440): 251-4.
[http://dx.doi.org/10.1038/nature12005] [PMID: 23486063]
[35]
Yuan Y, Cao D, Zhang Y, et al. Cryo-EM structures of MERS- CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun 2017; 8: 15092.
[http://dx.doi.org/10.1038/ncomms15092] [PMID: 28393837]
[36]
Aslow K, Stanberry LR, Le Duc JAW. Viral infections of humans.US: Springer 2014.
[37]
Conzade R, Grant R, Malik MR, et al. Reported direct and indirect contact with dromedary camels among laboratory-confirmed MERS-CoV cases. Viruses 2018; 10(8): 1-10.
[http://dx.doi.org/10.3390/v10080425] [PMID: 30104551]
[38]
Sabir JS, Lam TTY, Ahmed MM, et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 2016; 351(6268): 81-4.
[http://dx.doi.org/10.1126/science.aac8608] [PMID: 26678874]
[39]
Al-Ahmadi K, Alahmadi S, Al-Zahrani A. Spatiotemporal clustering of Middle East respiratory syndrome coronavirus (MERS- CoV) incidence in Saudi Arabia, 2012-2019. Int J Environ Res Public Health 2019; 16(14): 1-14.
[http://dx.doi.org/10.3390/ijerph16142520] [PMID: 31311073]
[40]
Gossner C, Danielson N, Gervelmeyer A, et al. Human- dromedary camel interactions and the risk of acquiring zoonotic Middle East respiratory syndrome coronavirus infection. Zoonoses Public Health 2016; 63(1): 1-9.
[http://dx.doi.org/10.1111/zph.12171] [PMID: 25545147]
[41]
Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet 2015; 386(9997): 995-1007.
[http://dx.doi.org/10.1016/S0140-6736(15)60454-8] [PMID: 26049252]
[42]
Cauchemez S, Fraser C, Van Kerkhove MD, et al. Middle East respiratory syndrome coronavirus: Quantification of the extent of the epidemic, surveillance biases, and transmissibility. Lancet Infect Dis 2014; 14(1): 50-6.
[http://dx.doi.org/10.1016/S1473-3099(13)70304-9] [PMID: 24239323]
[43]
Breban R, Riou J, Fontanet A. Interhuman transmissibility of Middle East respiratory syndrome coronavirus: Estimation of pandemic risk. Lancet 2013; 382(9893): 694-9.
[http://dx.doi.org/10.1016/S0140-6736(13)61492-0] [PMID: 23831141]
[44]
Kim SH, Ko JH, Park GE, et al. Atypical presentations of MERS- CoV infection in immunocompromised hosts. J Infect Chemother 2017; 23(11): 769-73.
[http://dx.doi.org/10.1016/j.jiac.2017.04.004] [PMID: 28545936]
[45]
Drosten C, Seilmaier M, Corman VM, et al. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis 2013; 13(9): 745-51.
[http://dx.doi.org/10.1016/S1473-3099(13)70154-3] [PMID: 23782859]
[46]
Grant R, Malik MR, Elkholy A, Van Kerkhove MD. A review of asymptomatic and subclinical middle east respiratory syndrome coronavirus infections. Epidemiol Rev 2019; 41(1): 69-81.
[http://dx.doi.org/10.1093/epirev/mxz009] [PMID: 31781765]
[47]
Kim JE, Heo JH, Kim HO, et al. Neurological complications during treatment of Middle East respiratory syndrome. J Clin Neurol 2017; 13(3): 227-33.
[http://dx.doi.org/10.3988/jcn.2017.13.3.227] [PMID: 28748673]
[48]
Alfaraj SH, Al-Tawfiq JA, Altuwaijri TA, Alanazi M, Alzahrani N, Memish ZA. Middle East respiratory syndrome coronavirus transmission among health care workers: Implication for infection control. Am J Infect Control 2018; 46(2): 165-8.
[http://dx.doi.org/10.1016/j.ajic.2017.08.010] [PMID: 28958446]
[49]
Hui DS, Memish ZA, Zumla A. Severe acute respiratory syndrome vs. the Middle East respiratory syndrome. Curr Opin Pulm Med 2014; 20(3): 233-41.
[http://dx.doi.org/10.1097/MCP.0000000000000046] [PMID: 24626235]
[50]
Arabi YM, Balkhy HH, Hayden FG, et al. Middle East respiratory syndrome. N Engl J Med 2017; 376(6): 584-94.
[http://dx.doi.org/10.1056/NEJMsr1408795] [PMID: 28177862]
[51]
Alfaraj SH, Al-Tawfiq JA, Memish ZA. Middle East respiratory syndrome coronavirus (mers-cov) infection during pregnancy: Report of two cases & review of the literature. J Microbiol Immunol Infect 2019; 52(3): 501-3.
[http://dx.doi.org/10.1016/j.jmii.2018.04.005] [PMID: 29907538]
[52]
Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A. Middle East respiratory syndrome coronavirus: Risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis 2018; 18(8): e217-27.
[http://dx.doi.org/10.1016/S1473-3099(18)30127-0] [PMID: 29680581]
[53]
World Health Organization. Home care for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection presenting with mild symptoms and management of contacts: Interim guidance (No. WHO/MERS/IPC/18.1). 2018. Available from: https://apps.who.int/iris/handle/10665/272948
[54]
Alshukairi AN, Khalid I, Ahmed WA, et al. Antibody response and disease severity in healthcare worker MERS survivors. Emerg Infect Dis 2016; 22(6): 1113-5.
[http://dx.doi.org/10.3201/eid2206.160010] [PMID: 27192543]
[55]
ul Qamar M T, Alqahtani S M, Alamri M A, Chen L L. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal 2020; 313-9.
[http://dx.doi.org/10.1016/j.jpha.2020.03.009]
[56]
Jo S, Kim S, Shin D H, Kim M S. Inhibition of SARS-CoV 3CL protease by flavonoids. Journal of enzyme inhibition and medicinal chemistry 2020; 35(1): 145-51.
[57]
Kumar V, Tan K P, Wang Y M, Lin S W, Liang P H. Identification, synthesis and evaluation of SARS-CoV and MERS-CoV 3C- like protease inhibitors. Bioorganic & medicinal chemistry 2016; 24(13): 3035-42.
[58]
Zhou J, Fang L, Yang Z, Xu S, Lv M, et al. Identification of novel proteolytically inactive mutations in coronavirus 3C-like protease using a combined approach. The FASEB J 2019; 33(12): 14575-87.
[59]
Dong S, Sun J, Mao Z, Wang L, Lu YL, Li J. A guideline for homology modeling of the proteins from newly discovered betacoronavirus, 2019 novel coronavirus (2019-nCoV). J Med Virol 2020; 92(9): 1542-8.
[http://dx.doi.org/10.1002/jmv.25768] [PMID: 32181901]
[60]
Skoging U, Liljeström P. Role of the C-terminal tryptophan residue for the structure-function of the alphavirus capsid protein. J Mol Biol 1998; 279(4): 865-72.
[http://dx.doi.org/10.1006/jmbi.1998.1817] [PMID: 9642067]
[61]
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci 2016; 5: e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[62]
Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. Journal of medical virology 2020; 92(5): 479-90.
[http://dx.doi.org/10.1002/jmv.25707]
[63]
Rothwell JA, Urpi-Sarda M, Boto-Ordoñez M, et al. Systematic analysis of the polyphenol metabolome using the Phenol-Explorer database. Mol Nutr Food Res 2016; 60(1): 203-11.
[http://dx.doi.org/10.1002/mnfr.201500435] [PMID: 26310602]
[64]
Shimizu J F, Lima C S, Pereira C M, Bittar C, Batista M N, et al. Flavonoids from pterogyne nitens inhibit hepatitis C virus entry. Scientific reports 2017; 7(1): 1-9.
[http://dx.doi.org/10.1038/s41598-017-16336-y]
[65]
Ryu Y B, Jeong H J, Kim J H, Kim Y M, Park J Y, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition. Bioorganic & medicinal chemistry 2010; 18(22): 7940-7.
[66]
Ye G, Wang X, Tong X, Shi Y, Fu Z F, Peng G. Structural basis for inhibiting porcine epidemic diarrhea virus replication with the 3C-Like protease inhibitor GC376. Viruses 2020; 12(2): 1-15.
[67]
Theerawatanasirikul S, Kuo C J, Phetcharat N, Lekcharoensuk P. In silico and in vitro analysis of small molecules and natural compounds targeting the 3CL protease of feline infectious peritonitis virus. Antiviral research 2020; 174: 1-9.
[68]
Muramatsu T, Takemoto C, Kim YT, Wang H, Nishii W, et al. SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity. Proceedings of the National Academy of Sciences. 12997-3002.
[http://dx.doi.org/10.1073/pnas.1601327113]
[69]
Russo M, Moccia S, Spagnuolo C, Tedesco I, Russo G L. Roles of flavonoids against coronavirus infection. Chemico-biological interactions 2020; 328: 1-12.
[70]
Russo GL, Tedesco I, Spagnuolo C, Russo M. Antioxidant polyphenols in cancer treatment: Friend, foe or foil? Semin Cancer Biol 2017; 46: 1-13.
[http://dx.doi.org/10.1016/j.semcancer.2017.05.005] [PMID: 28511887]
[71]
Spagnuolo C, Moccia S, Russo G L. Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Europ J Medi Chem 2018; 153: 105-15.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.001]
[72]
Mierziak J, Kostyn K, Kulma A. Flavonoids as important molecules of plant interactions with the environment. Molecules 2014; 19(10): 16240-65.
[http://dx.doi.org/10.3390/molecules191016240]
[73]
Nabavi S M, Šamec D, Tomczyk M, Milella L, Russo D, et al. Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering. Biotechnol Adv 2020; 38: 1-15.
[74]
Ferrer JL, Austin MB, Stewart C Jr, Noel JP. Structure and function of enzymes involved in the biosynthesis of phenylpropanoids. Plant Physiol Biochem 2008; 46(3): 356-70.
[http://dx.doi.org/10.1016/j.plaphy.2007.12.009] [PMID: 18272377]
[75]
Lalani S, Poh C L. Flavonoids as antiviral agents for Enterovirus A71 (EV-A71). Viruses 2020; 12(2): 1-34.
[76]
Lotito SB, Zhang WJ, Yang CS, Crozier A, Frei B. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med 2011; 51(2): 454-63.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.04.032] [PMID: 21571063]
[77]
Zakaryan H, Arabyan E, Oo A, Zandi K. Flavonoids: Promising natural compounds against viral infections. Arch Virol 2017; 162(9): 2539-51.
[http://dx.doi.org/10.1007/s00705-017-3417-y] [PMID: 28547385]
[78]
Phan C W, Sabaratnam V, Yong W K, Abd Malek S N. The role of chalcones: Helichrysetin, xanthohumol, and flavokawin-C in promoting neurite outgrowth in PC12 Adh cells. Natural product research 2018; 32(10): 1229-33.
[http://dx.doi.org/10.1080/14786419.2017.1331226]
[79]
Ho YF. . Cytotoxic effect of helichrysetin on cancer cell lines and its mechanisms/Ho Yen Fong. Doctoral dissertation 2017.
[80]
Xu-Dong H O U, Li-Lin S O N G, Yun-Feng C A O, Yi-Nan W A N G, Qi Z H O U, et al. Pancreatic lipase inhibitory constituents from Fructus Psoraleae. Chinese journal of natural medicines 2020; 18(5): 369-78.
[81]
Yadav VR, Prasad S, Sung B, Aggarwal BB. The role of chalcones in suppression of NF-κB-mediated inflammation and cancer. Int Immunopharmacol 2011; 11(3): 295-309.
[http://dx.doi.org/10.1016/j.intimp.2010.12.006] [PMID: 21184860]
[82]
Sehnal D, Rose AS, Koča J, Burley SK, Velankar S. Mol* towards a common library and tools for web molecular graphics. Proceedings of the workshop on molecular graphics and visual analysis of molecular data. 29-33.
[83]
Struijs K, Vincken J P, Doeswijk T G, Voragen A G, Gruppen H. The chain length of lignan macromolecule from flaxseed hulls is determined by the incorporation of coumaric acid glucosides and ferulic acid glucosides. Phytochem 2009; 70(2): 262-9.
[http://dx.doi.org/10.1016/j.phytochem.2008.12.015]
[84]
Oomah B D. Flaxseed by-products. Food wastes and by-products: Nutraceutical and health potential 2020; 267-89.
[http://dx.doi.org/10.1002/9781119534167.ch9]
[85]
Massi A, Bortolini O, Ragno D, et al. Research progress in the modification of quercetin leading to anticancer agents. Molecules 2017; 22(8): 1-27.
[http://dx.doi.org/10.3390/molecules22081270]
[86]
Nguyen T T H, Woo H J, Kang H K, Kim Y M, Kim D W, et al. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol Lett 2012; 34(5): 831-8.
[87]
Yonesi M, Rezazadeh A. Plants as a prospective source of natural anti-viral compounds and oral vaccines against COVID-19. Coronavirus. 2020; 1-31.
[88]
Balasuriya BN, Rupasinghe HV. Plant flavonoids as angiotensin converting enzyme inhibitors in regulation of hypertension. Funct Food Health Dis 2011; 1(5): 172-88.
[http://dx.doi.org/10.31989/ffhd.v1i5.132]
[89]
Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA. Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74(4): 418-25.
[http://dx.doi.org/10.1093/ajcn/74.4.418] [PMID: 11566638]
[90]
Dong W, Wei X, Zhang F, et al. A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways. Sci Rep 2014; 4(1): 7237.
[http://dx.doi.org/10.1038/srep07237] [PMID: 25429875]
[91]
Sheahan TP, Sims AC, Leist SR, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020; 11(1): 222.
[http://dx.doi.org/10.1038/s41467-019-13940-6] [PMID: 31924756]
[92]
Solnier J, Fladerer JP. Flavonoids: A complementary approach to conventional therapy of COVID-19? Phytochem Rev 2020; 1-23.
[http://dx.doi.org/10.1007/s11101-020-09720-6] [PMID: 32982616]

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