Structure-based virtual screening and molecular dynamics of phytochemicals derived from Saudi medicinal plants to identify potential COVID-19 therapeutics

被引:45
作者
Alamri, Mubarak A. [1 ]
Altharawi, Ali [1 ]
Alabbas, Alhumaidi B. [1 ]
Alossaimi, Manal A. [1 ]
Alqahtani, Safar M. [1 ]
机构
[1] Prince Sattam Bin Abdulaziz Univ, Dept Pharmaceut Chem, Coll Pharm, POB 173, Al Kharj 11942, Saudi Arabia
关键词
Antiviral; COVID-19; MD simulation; SARS-CoV-2; Virtual screening; Protease; CORONAVIRUS; INHIBITORS; EXTRACTS; PROTEIN;
D O I
10.1016/j.arabjc.2020.08.004
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Coronavirus disease 2019 (COVID-19) has affected almost every country in the world by causing a global pandemic with a high mortality rate. Lack of an effective vaccine and/or antiviral drugs against SARS-CoV-2, the causative agent, has severely hampered the response to this novel coronavirus. Natural products have long been used in traditional medicines to treat various diseases, and purified phytochemicals from medicinal plants provide a valuable scaffold for the discovery of new drug leads. In the present study, we performed a computational screening of an in-house database composed of similar to 1000 phytochemicals derived from traditional Saudi medicinal plants with recognised antiviral activity. Structure-based virtual screening was carried out against three druggable SARS-CoV-2 targets, viral RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like cysteine protease (3CL(pro)) and papain like protease (PLpro) to identify putative inhibitors that could facilitate the development of potential anti-COVID-19 drug candidates. Computational analyses identified three compounds inhibiting each target, with binding affinity scores ranging from -9.9 to -6.5 kcal/mol. Among these, luteolin 7-rutinoside, chrysophanol 8-(6-galloylglucoside) and kaempferol 7-(6 ''-galloylglucoside) bound efficiently to RdRp, while chrysophanol 8-(6-galloylglucoside), 3,4,5-tri-O-galloylquinic acid and mulberrofuran G interacted strongly with 3CL(pro), and withanolide A, isocodonocarpine and calonysterone bound tightly to PLpro. These potential drug candidates will be subjected to further in vitro and in vivo studies and may assist the development of effective anti-COVID-19 drugs. (c) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
引用
收藏
页码:7224 / 7234
页数:11
相关论文
共 43 条
[1]   Moroccan Medicinal plants as inhibitors against SARS-CoV-2 main protease: Computational investigations [J].
Aanouz, I. ;
Belhassan, A. ;
El-Khatabi, K. ;
Lakhlifi, T. ;
El-Idrissi, M. ;
Bouachrine, M. .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2021, 39 (08) :2971-2979
[2]   Traditional use of ethnomedicinal native plants in the Kingdom of Saudi Arabia [J].
Aati, Hanan ;
El-Gamal, Ali ;
Shaheen, Hamdy ;
Kayser, Oliver .
JOURNAL OF ETHNOBIOLOGY AND ETHNOMEDICINE, 2019, 15 (1)
[3]   Pharmacoinformatics and molecular dynamic simulation studies to identify potential small-molecule inhibitors of WNK-SPAK/OSR1 signaling that mimic the RFQV motifs of WNK kinases [J].
Alamri, Mubarak A. .
ARABIAN JOURNAL OF CHEMISTRY, 2020, 13 (04) :5107-5117
[4]   Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs [J].
Anand, K ;
Ziebuhr, J ;
Wadhwani, P ;
Mesters, JR ;
Hilgenfeld, R .
SCIENCE, 2003, 300 (5626) :1763-1767
[5]  
[Anonymous], 2021, FDA Statement: Coronavirus (COVID-19) Update: FDA takes steps to streamline path for COVID-19 screening tools, provides information to help groups establishing testing programs
[6]   In vitro evaluation of novel antiviral activities of 60 medicinal plants extracts against hepatitis B virus [J].
Arbab, Ahmed Hassan ;
Parvez, Mohammad Khalid ;
Al-Dosari, Mohammed Salem ;
Al-Rehaily, Adnan Jathlan .
EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2017, 14 (01) :626-634
[7]  
Babel O., 2011, J CHEMINFORMATICS, V3, P33
[8]   The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds [J].
Baez-Santos, Yahira M. ;
St John, Sarah E. ;
Mesecar, Andrew D. .
ANTIVIRAL RESEARCH, 2015, 115 :21-38
[9]  
Bitencourt-Ferreira G, 2019, METHODS MOL BIOL, V2053, P93, DOI 10.1007/978-1-4939-9752-7_7
[10]   Emerging coronaviruses: Genome structure, replication, and pathogenesis [J].
Chen, Yu ;
Liu, Qianyun ;
Guo, Deyin .
JOURNAL OF MEDICAL VIROLOGY, 2020, 92 (04) :418-423