Tianjiao Li
ABSTRACT
SARS-CoV-2 has been reported as an international public health emergency by the World Health Organization. However, at present, there is anabsence of safe and effective therapeutic drugs.S protein and Mpro are important functional proteins forSARS-CoV-2 and can be chosen as targets for screening active compounds. To analyzealliin and allicin binding modewith SARS-CoV-2S/ACE2 and SARS-CoV-2 Main protease (Mpro) by molecular docking technique and molecular dynamics simulation, and the intervention effect of alliin and allicin on SARS-CoV-2 was speculated. The results showed that alliin and allicin could block the binding of SARS-CoV-2S/ACE2 and inhibit SARS-CoV-2Mpro, and the binding effect of alliin was stronger than allicin. This study predicts that alliin and allicin can prevent and treat SARS-CoV-2 by interfering with the complex of SARS-CoV-2S/ACE2 and SARS-CoV-2Mpro, which provide a reference for the research and development of anti-SARS-CoV-2 active compounds.
- Gorbalenya A E, Baker S C, Baric R S, The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. NPG Open Access. 5(4), 536-544. 2020.Google Scholar
- Zheng J. SARS-CoV-2: an emergingcoronavirus that causes a global threat. International Journal of Biological Sciences. 16(10), 1678-1685. 2020.Google ScholarCross Ref
- Xintian, Xu, Ping, Evolution of the novel coronavirus from the ongoing wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China(Life Sciences). 63(3), 457-460. 2020.Google Scholar
- Davis M A, Delaney J, Patel C, Nelfinavir is effective against cervical cancer tumors: a potential treatment modality in resource limited settings. Gynecologic Oncology. 139(1), 191-196. 2015.Google ScholarCross Ref
- Lan J, Ge J, Yu J, Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 581(7807), 215-220. 2020.Google ScholarCross Ref
- Xinliu, Xiu-Jiewang. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. Journal of Genetics and Genomics. 2(47), 119-121. 2020.Google Scholar
- Jessica, Bradley, Chelsea, Garlic-derived organic polysulfides and myocardial protection. Journal of Nutrition. 146(2), 403-405. 2016.Google ScholarCross Ref
- Ji T J, Kim W T. Study on radioprotection of alliin and damage mechanism in hepatocyte after irradiation. 39(4), 623-630. 2016.Google Scholar
- Borlinghaus J, Albrecht F, Gruhlke M, Allicin: chemistry and biological properties. Molecules.19(8), 12591-12618. 2014.Google ScholarCross Ref
- Sekh, Abdul, Nasim, Alliin obtained from leaf extract of garlic grown underinsituconditions possess higher therapeutic potency as analyzed in alloxan-induced diabetic rats. Pharmaceutical Biology. 49(4), 416-421. 2011.Google ScholarCross Ref
- Zhai B, Zhang C, Sheng Y, Hypoglycemic and hypolipidemic effect of s-allyl-cysteine sulfoxide (alliin) in dio mice. Scientific Reports. 8(1), 3527-3530. 2018.Google ScholarCross Ref
- Yoshimoto N, Onuma M, Mizuno S, Identification of a flavin-containing s-oxygenating monooxygenase involved in alliin biosynthesis in garlic. Plant Journal for Cell & Molecular Biology. 83(6), 941-951. 2015.Google ScholarCross Ref
- Naoko Y, Kazuki S. S-alk(en)ylcysteine sulfoxides in the genus allium: proposed biosynthesis, chemical conversion, and bioactivities. Journal of Experimental Botany.70(16), 4123-4137. 2019.Google ScholarCross Ref
- Lefer, David J. PL07 Diallyl trisulfide (DATS) protects against heart failure via eNOS activation and nitric oxide mediated cardioprotection. Nitric Oxide. 31(2), S14. 2013.Google Scholar
- Yamaguchi Y, Kumagai H. Characteristics, biosynthesis, decomposition, metabolism and functions of the garlic odour precursor, S-allyl-L-cysteine sulfoxide. Experimental and Therapeutic Medicine. 19(2), 1528-1535. 2020.Google Scholar
- Lai K C, Hsu S C, Yang J S, Diallyl trisulfide inhibits migration, invasion and angiogenesis of human colon cancer HT-29 cells and umbilical vein endothelial cells, and suppresses murine xenograft tumour growth. Journal of Cellular & Molecular Medicine. 19(2), 474-484. 2015.Google ScholarCross Ref
- Yin X, Zhang R, Feng C, Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and mek-erk pathways in human esophageal squamous cell carcinoma. Oncology Reports. 32(4), 1748-1756. 2014.Google ScholarCross Ref
- Yamaguchi Y, Honma R, Yazaki T, Sulfuric odor precursor S-Allyl-l-Cysteine sulfoxide in garlic induces detoxifying enzymes andprevents hepatic Injury. Antioxidants. 8(9), 385-386. 2019.Google ScholarCross Ref
- Kim S H, Lee I C, Ko J W, Diallyl disulfide prevents cyclophosphamide-induced hemorrhagic cystitis in rats through the inhibition of oxidative damage, MAPKs, and NF-κB Pathways. Biomolecules & Therapeutics.23(2), 180-188. 2015.Google ScholarCross Ref
- Donma M M , Donma O .The Effects of allium sativum on immunity within the scope of COVID-19 infection [J]. Medical Hypotheses, 144:109934. 2020.Google ScholarCross Ref
- Yan R, Zhang Y, Li Y, Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2. Science. 367(6485), 1444-1448. 2020.Google ScholarCross Ref
- Badavath VN, Kumar A, Samanta PK, Determination of potential inhibitors based on isatin derivatives against SARS-CoV-2 main protease (mpro): a molecular docking, molecular dynamics and structure-activity relationship studies. J Biomol Struct Dyn. 40(7), 3110-3128. 2022.Google ScholarCross Ref
- Badieyan S, Bevan D R, Zhang C. Study and design of stability in GH5 cellulases. Biotechnology and Bioengineering. 109(1), 31-44. 2012.Google ScholarCross Ref
- Purmonen M, Valjakka J, Takkinen K, Molecular dynamics studies on the thermostability of family II xylanases. Protein Engineering Design and Selection. 20(11), 551-559. 2007.Google ScholarCross Ref
Index Terms
- Analysis of the mechanism of alliin and allicin against SARS-CoV-2S/ACE2 and SARS-CoV-2 Mpro based on molecular docking and molecular dynamics
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