Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors
Ahmad Sattari, Ali Ramazani, Hamideh Aghahosseini
doi:10.21203/rs.3.rs-37994/v1
Today, nding potential therapeutics for COVID-19 caused by the widespread transmission of SARS-CoV-2 has become a global challenge. Molecular docking investigation of the therapeutic potential of marketed drugs is a fast and cost effective approach to provide a solution to this problem. In this study, docking simulations performed on the reported structure of the virus main protease, 3CLpro, to identify potential inhibitors. Accordingly, a database of 50 synthetic compounds including approved drugs and those undergoing clinical trials, and 40 natural compounds particularly those employed in traditional Iranian medicine was constructed. The results indicated that the anti-in ammatory drugs, Licofelone acyl glucuronide and delta-bilirubin, and natural compounds such as kappa-carrageenan conformer and beta-D-galactopyranosyl with minimal side-effects, according to in-vitro studies, are good candidates to block the enzymatic activity of SARS-CoV-2 3CLpro. Moreover, the compound 1 could be a potential drug candidate for COVID-19 due to its favorable interactions with the 3CLpro.
Supplementary Files This is a list of supplementary les associated with this preprint. Click to download.
SupportingInformation.docx GraphicalAbstract.tif
References
Aa, Agrawal, Garron, Tao, Peng et al., Proc. Natl. Acad. Sci
Ad, Han, Penn-Nicholson, Cho, Ge et al., None, Virology
Ad, Hui, Azhar, Madani, Ntoumi et al., None, Int. J. Infect. Dis
Ad, Hui, Azhar, Madani, Ntoumi et al., WHO Statement Regarding Cluster of Pneumonia Cases in
Aj, Kahn, Mcintosh ; Geller, Varbanov, Duval, None, Pediatr. Infect. Dis. J
Aj. Cohen ; Zhou, Yang, Wang, Hu, Zhang et al., None, Nature
Alikhani, Razzaghi-Asl, Ramazani, Hosseinzadeh, None, J. Mol. Struct
Almeida, Berry, Cunningham, Hamre, Hofstad et al., None, Adv. Virus Res. (Elsevier)
Ameri, Heydarirad, Mahdavi, Jafari, Ghobadi et al., None, eM. Abolhassani, Arch. Med. Sci
Anand, Ziebuhr, Wadhwani, Mesters, Hilgenfeld, None, Science
Ar, Dizaji, Rezaie Kehkhaie, Taqi Khammar, Shirazinia, None, Int J Plant Sci Hor
Asadi-Samani, Moradi, Bahmani, Shahrani, None, Int.J. PharmTech Res
Ascone, Sakidja, None, Int. J. Comput Biol. Drug Des
Bosch, Van Der Zee, De Haan, Rottier, None, J. Virol
Choubey, Varughese, Kumar, Beniwal, None, Pharm. Pat. Anal
Covid, Global Cases by Johns Hopkins CSSE. Вилучено з
Fehr, Perlman, Coronaviruses
Gaillard, None, J. Chem. Inf. Model
Gao, Tian, Yang, None, Biosci. Trends
Goldsmith, Tatti, Ksiazek, Rollin, Comer et al., None, Emerg. Infect. Dis
Grassauer, Eva, Us, None
Ji, Wang, Zhao, Zai, Li, None, J. Med. Virol
Johnson, Mesecar ; Kumar, Tan, Wang, Lin et al., None, Bioorg. Med. Chem. Lett
Liu, Zhang, Jin, Yang, Rao, The crystal structure of COVID-19 main protease in complex with an inhibitor N3,
doi:10.2210/PDB6LU7/PDBLu, Mahindroo, Liang, Peng, Kuo et al., None, Acta Crystallogr., Sect. D: Biol. Crystallogr
Ma, Fu, Khojasteh, Dalvie, Zhang, None, J. Med. Chem
Masters, Eagon, Heying, None, J. Mol. Graph. Model
Morris, Huey, Lindstrom, Sanner, Belew et al., None, J. Comput. Chem
Naoi, Shamoto-Nagai, Maruyama, None, Future Neurol
Neuman, Adair, Yoshioka, Quispe, Orca et al., None, J. Virol
Neuman, Kiss, Kunding, Bhella, Baksh et al., None, J. Struct. Biol
Organization, Laboratory testing of human suspected cases of novel coronavirus ( nCoV) infection: interim guidance" can be found under www
Orita, Ohno, Warizaya, Amano, Niimi, None, Methods in enzymology
Pillaiyar, Manickam, Namasivayam, Hayashi, Jung ; Ba et al., None, J. Med. Chem
Price, Gould, Marsh, None, J. Chem. Educ
Shu, Mccauley, None, Euro Surveill
Trott, Olson, None, J. Comput. Chem
Wallace, Laskowski, Thornton, None, Protein Eng. Des. Sel
Wang, Chen, Lu, Chen, Zhang, None, Biosci. Trends
Winther, Hansen, Campbell-Tofte, None, Botanics
Wong, Li, Lau, Woo, None, Viruses
Wu, Liu, Yang, Zhang, Zhong et al., None, Acta Pharm. Sin. B
Yang, Yang, Ding, Liu, Lou et al., Proc. Natl. Acad. Sci
Zhu, Zhang, Wang, Li, Yang et al., None, N Engl. J. Med
Zhu, Zhang, Ye, Li, Zhou et al., None, Biol. Pharm. Bull
DOI record:
{
"DOI": "10.21203/rs.3.rs-37994/v1",
"URL": "http://dx.doi.org/10.21203/rs.3.rs-37994/v1",
"abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Today, finding potential therapeutics for COVID-19 caused by the widespread transmission of <jats:italic>SARS-CoV-2 </jats:italic>has become a global challenge. Molecular docking investigation of the therapeutic potential of marketed drugs is a fast and cost effective approach to provide a solution to this problem. In this study, docking simulations performed on the reported structure of the virus main protease, <jats:italic>3CLpro</jats:italic>,<jats:italic> </jats:italic>to identify potential inhibitors. Accordingly, a database of 50 synthetic compounds including approved drugs and those undergoing clinical trials, and 40 natural compounds particularly those employed in traditional Iranian medicine was constructed. The results indicated that the anti-inflammatory drugs, <jats:italic>Licofelone acyl glucuronide</jats:italic> and <jats:italic>delta-bilirubin</jats:italic>, and natural compounds such as <jats:italic>kappa-carrageenan conformer</jats:italic> and <jats:italic>beta-D-galactopyranosyl</jats:italic> with minimal side-effects, according to <jats:italic>in-vitro</jats:italic> studies, are good candidates to block the enzymatic activity of <jats:italic>SARS-CoV-2 3CLpro</jats:italic>. Moreover, the <jats:italic>compound 1</jats:italic> could be a potential drug candidate for <jats:italic>COVID-19</jats:italic> due to its favorable interactions with the <jats:italic>3CLpro. </jats:italic></jats:p>",
"accepted": {
"date-parts": [
[
2020,
6,
26
]
]
},
"author": [
{
"affiliation": [
{
"name": "University of Zanjan"
}
],
"family": "Sattari",
"given": "Ahmad",
"sequence": "first"
},
{
"affiliation": [
{
"name": "University of Zanjan"
}
],
"family": "Ramazani",
"given": "Ali",
"sequence": "additional"
},
{
"affiliation": [
{
"name": "University of Zanjan"
}
],
"family": "Aghahosseini",
"given": "Hamideh",
"sequence": "additional"
}
],
"container-title": [],
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2020,
6,
30
]
],
"date-time": "2020-06-30T01:18:43Z",
"timestamp": 1593479923000
},
"deposited": {
"date-parts": [
[
2022,
7,
28
]
],
"date-time": "2022-07-28T21:46:19Z",
"timestamp": 1659044779000
},
"group-title": "In Review",
"indexed": {
"date-parts": [
[
2024,
3,
3
]
],
"date-time": "2024-03-03T13:46:33Z",
"timestamp": 1709473593418
},
"institution": [
{
"name": "Research Square"
}
],
"is-referenced-by-count": 2,
"issued": {
"date-parts": [
[
2020,
6,
30
]
]
},
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "unspecified",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2020,
6,
30
]
],
"date-time": "2020-06-30T00:00:00Z",
"timestamp": 1593475200000
}
}
],
"link": [
{
"URL": "https://www.researchsquare.com/article/rs-37994/v1",
"content-type": "text/html",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://www.researchsquare.com/article/rs-37994/v1.html",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "8761",
"original-title": [],
"posted": {
"date-parts": [
[
2020,
6,
30
]
]
},
"prefix": "10.21203",
"published": {
"date-parts": [
[
2020,
6,
30
]
]
},
"publisher": "Research Square Platform LLC",
"reference-count": 0,
"references-count": 0,
"relation": {
"is-preprint-of": [
{
"asserted-by": "subject",
"id": "10.1007/s13738-021-02235-7",
"id-type": "doi"
}
]
},
"resource": {
"primary": {
"URL": "https://www.researchsquare.com/article/rs-37994/v1"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [],
"subtitle": [],
"subtype": "preprint",
"title": "Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors",
"type": "posted-content"
}
