Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors
et al., Research Square, doi:10.21203/rs.3.rs-37994/v1, Jun 2020
In silico study identifying kappa-carrageenan and other compounds as potential candidates for SARS-CoV-2 inhibition.
18 preclinical studies support the efficacy of iota-carrageenan for COVID-19:
1.
Krylova et al., Carrageenans and the Carrageenan-Echinochrome Complex as Anti-SARS-CoV-2 Agents, International Journal of Molecular Sciences, doi:10.3390/ijms26136175.
2.
Rohilla et al., Algae Polysaccharides (Carrageenan and Alginate)—A Treasure-Trove of Antiviral Compounds: An In Silico Approach to Identify Potential Candidates for Inhibition of S1-RBD Spike Protein of SARS-CoV-2, Stresses, doi:10.3390/stresses3030039.
3.
Thet, H., The potential of carrageenan for the drug discovery of COVID-19 via molecular docking with angiotensin-converting enzyme 2 (ACE2) and the main protease (Mpro) of SARS-CoV-2, Journal of Bioinformatics and Genomics, doi:10.18454/jbg.2022.18.2.001.
4.
Alsaidi et al., Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model, Marine Drugs, doi:10.3390/md19080418.
5.
Sattari et al., Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors, Research Square, doi:10.21203/rs.3.rs-37994/v1.
6.
Hoffmann et al., Controlling the Sulfation Density of Glycosaminoglycan Glycopolymer Mimetics Enables High Antiviral Activity against SARS-CoV-2 and Reduces Anticoagulant Activity, Biomacromolecules, doi:10.1021/acs.biomac.5c00576.
7.
Yathindranath et al., Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection, International Journal of Nanomedicine, doi:10.2147/IJN.S448005.
8.
Setz et al., Iota-Carrageenan Inhibits Replication of the SARS-CoV-2 Variants of Concern Omicron BA.1, BA.2 and BA.5, Nutraceuticals, doi:10.3390/nutraceuticals3030025.
9.
Meister et al., Virucidal activity of nasal sprays against severe acute respiratory syndrome coronavirus-2, Journal of Hospital Infection, doi:10.1016/j.jhin.2021.10.019.
10.
Bovard et al., Iota-carrageenan extracted from red algae is a potent inhibitor of SARS-CoV-2 infection in reconstituted human airway epithelia, Biochemistry and Biophysics Reports, doi:10.1016/j.bbrep.2021.101187.
11.
Fröba et al., Iota-Carrageenan Inhibits Replication of SARS-CoV-2 and the Respective Variants of Concern Alpha, Beta, Gamma and Delta, International Journal of Molecular Sciences, doi:10.3390/ijms222413202.
12.
Varese et al., Iota-carrageenan prevents the replication of SARS-CoV-2 on an in vitro respiratory epithelium model, bioRxiv, doi:10.1101/2021.04.27.441512.
13.
Morokutti-Kurz et al., Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro, PLoS ONE, doi:10.1371/journal.pone.0237480.
14.
Song et al., Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2, Food & Function, doi:10.1039/D0FO02017F.
Sattari et al., 29 Jun 2020, preprint, 3 authors.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Repositioning Therapeutics for COVID-19: Virtual Screening of the Potent Synthetic and Natural Compounds as SARS-CoV-2 3CLpro Inhibitors
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
Beck, Shin, Choi, Park, Kang, None, doi:10.1101/2020.01.31.929547
Bosch, Van Der Zee, De Haan, Rottier, None, J. Virol
Chang, Tung, Lee, Chen, Hsiao et al., None, doi:10.20944/preprints202002.0242.v1
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/PDB
Lu, 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
Sekhar, None, doi:10.20944/preprints202002.0418.v1
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
Wang, None, doi:10.26434/chemrxiv.11875446.v1
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
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"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>",
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