Structure-based inhibitor screening of natural products against NSP15 of SARS-CoV-2 revealed thymopentin and oleuropein as potent inhibitors

Vijayan, Ramachandran; Gourinath, S.

doi:10.1007/s42485-021-00059-w

Cited by 20 publications

(15 citation statements)

References 50 publications

(134 reference statements)

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“…In addition, oleuropein interacted highly favorably with Nsp15, a SARS-CoV-2 endoribonuclease, and formed electrostatic contacts with 11 residues, Van der Waals contacts with 5 residues, and a total of 4 Hbonds with 3 residues of this enzyme. It has been further reported that the functional groups that contribute most to the formation of the H-bonds in this interaction were the -OH and 3-methylene-4H-pyran moieties of the oleuropein molecule (Vijayan and Gourinath, 2021). In a drug repurposing study performed with the Glide docking module, oleuropein exhibited -9.21 kcal mol -1 (in the absence of Mg 2+ ) and -6.07 kcal mol -1 (in the presence of Mg +2 ) docking scores against the RdRp enzyme (Kandeel et al, 2020).…”

Section: Resultsmentioning

confidence: 90%

Fenolik Bileşik Oleuropein ve Hidroliz Ürünü 3-Hidroksitirozol'ün SARS-CoV-2'nin Bazı Yapısal ve Yapısal Olmayan Proteinlerine Karşı In Siliko Etkinliği

İstifli

2021

Türk Tarım Ve Doğa Bilimleri Dergisi

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The novel corona virus has infected nearly 163 million people globally as of May 2021 and caused death of more than 3.3 million patients. Despite intense efforts, however, a small molecule with full therapeutic potential has not been developed in the treatment of SARS-CoV-2. The aim of this study was to investigate the inhibitory potentials of oleuropein and its hydrolysis product 3-hydroxytyrosol against spike glycoprotein, papain-like protease, main protease and RNA-dependent RNA polymerase of SARS-CoV-2 using molecular modelling simulations. Compared to 3-hydroxytyrosol, oleuropein showed stronger binding affinity to all targets in docking, and its affinity to Mpro (-7.0 kcal mol -1 ) and RdRp (-8.0 kcal mol -1 ) was quite high. Despite the Mpro-oleuropein complex, the RdRp-oleuropein complex showed a highly stable binding in 15-ns molecular dynamics based on root-mean-square-deviation (0.14 -0.32 nm) and hydrogen bond numbers (6.85). The intracellular targets of oleuropein covered various proteases (17%), enzymes (16%), family A G protein-coupled receptors (11%), kinases (10%) and other cytosolic proteins (10%), however, probabilistic analysis showed that oleuropein was unlikely (p = 0 -0.22) to bind these targets. ADMET profile showed that, with few exceptions, oleuropein has the physicochemistry that should be present in a drug molecule. In conclusion, oleuropein binds tightly to the active site of RdRp and could inhibit this enzyme. Oleuropein may be used alone or in combination with replicase inhibitors such as remdesivir or favipiravir in the treatment of COVID-19. Additional in vitro binding assays and in vivo efficacy studies are needed to prove our findings.

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Section: Resultsmentioning

confidence: 90%

Fenolik Bileşik Oleuropein ve Hidroliz Ürünü 3-Hidroksitirozol'ün SARS-CoV-2'nin Bazı Yapısal ve Yapısal Olmayan Proteinlerine Karşı In Siliko Etkinliği

İstifli

2021

Türk Tarım Ve Doğa Bilimleri Dergisi

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“…The endoribonuclease activity of NSP15 interferes with the innate immune response of the host. All the AGP derivatives and reference compounds have interacted with some of the active site amino acid residues of NSP15: His-235, Asp-240, Ser-242, His-243, Gln-245, Leu-246, Gly-248, His-250, Asn-278, Lys-290, Glu-340, Thr-343, Lys345, and Leu-346 as suggested by Vijayan and Gourinath (2021) [ 37 ]. NSP15 is a known anti-viral drug target, and its active site constitutes the catalytic triad His-235, His-250, and Lys-290.…”

Section: Discussionmentioning

confidence: 99%

Molecular docking unveils the potential of andrographolide derivatives against COVID-19: an in silico approach

Veerasamy

Karunakaran

2022

Journal of Genetic Engineering and Biotechnology

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Background The recent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection cause high mortality and there is an emergency need to develop a specific drug to treat the novel coronavirus disease, COVID-19. However, some natural and synthetic products with action against SARS-CoV-2 have been reported in recent research, there is no specific drug available for treating COVID-19. In the present study, molecular interaction analysis was performed for 16 semisynthetic andrographolides (AGP) against 5 SARS-CoV-2 enzymes main protease (Mpro, PDB: 6LU7), papain-like protease (PLpro, PDB: 6WUU), spike glycoprotein (S, PDB: 6VXX), NSP15 endoribonuclease (NSP15, PDB: 6VWW), and RNA-dependent RNA polymerase (RdRp, PDB: 6M71). Moreover, the compounds pharmacokinetic and toxic profiles were also analyzed using computational tools. Results The protein−ligand docking score (kcal/mol) revealed that all the tested AGP derivatives showed a better binding affinity towards all the tested enzymes than hydroxychloroquine (HCQ). Meanwhile, all the tested AGP derivatives showed a better binding score with RdRp and S than remdesivir (REM). Interestingly, compounds 12, 14, and 15 showed a better binding affinity towards the all the tested enzyme than AGP, REM, and HCQ. AGP-16 had shown − 8.7 kcal/mol binding/docking score for Mpro, AGP-15 showed − 8.6 kcal/mol for NSP15, and AGP-10, 13, and 15 exhibited − 8.7, − 8.9, and − 8.7 kcal/mol, respectively, for S. Conclusion Overall results of the present study concluded that AGP derivatives 14 and 15 could be the best ‘lead’ candidate for the treatment against SARS-CoV-2 infection. However, molecular dynamic studies and pharmacological screenings are essential to developing AGP derivatives 14 and 15 as a drug against COVID-19.

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“…The antiviral activity of olive leaf metabolites against SARS-CoV-2 was reported in several in silico computational studies. Several viral targets were tested, such as viral proteases (Mpro/3CLpro, PLpro), TLRs, ACE2, RBD, NSP15, HSPA5 SBD β , TMPRSS2, S protein, and furin ( Yu et al, 2020a ; Yu et al, 2020b ; Derosa et al, 2020 ; Elfiky, 2020 ; Hashem, 2020 ; Hu et al, 2020 ; Jena et al, 2020 ; Khaerunnisa et al, 2020 ; Sampangi-Ramaiah et al, 2020 ; Shawky et al, 2020 ; Suručić et al, 2020 ; Vardhan and Sahoo, 2020 ; Vijayan and Gourinath, 2020 ; Khan et al, 2021 ) ( Table 1 ).…”

Section: Biology Reviewmentioning

confidence: 99%

Olive Leaves as a Potential Phytotherapy in the Treatment of COVID-19 Disease; A Mini-Review

Abdelgawad

Hassab²,

Abourehab

et al. 2022

Front. Pharmacol.

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Beginning from December 2019, widespread COVID-19 has caused huge financial misfortunes and exceptional wellbeing emergencies across the globe. Discovering an effective and safe drug candidate for the treatment of COVID-19 and its associated symptoms became an urgent global demand, especially due to restricted information that has been discharged with respect to vaccine efficacy and safety in humans. Reviewing the recent research, olive leaves were selected as a potential co-therapy supplement for the treatment and improvement of clinical manifestations in COVID-19 patients. Olive leaves were reported to be rich in phenolic compounds such as oleuropein, hydroxytyrosol, verbascoside, apigenin-7-O-glucoside, and luteolin-7-O-glucoside and also triterpenoids such as maslinic, ursolic, and oleanolic acids that have been reported as anti–SARS-CoV-2 metabolites in recent computational and in vitro studies. In addition, olive leaf extract was previously reported in several in vivo studies for its anti-inflammatory, analgesic, antipyretic, immunomodulatory, and antithrombotic activities which are of great benefit in the control of associated inflammatory cytokine storm and disseminated intravascular coagulation in COVID-19 patients. In conclusion, the described biological activities of olive leaves alongside their biosafety, availability, and low price make them a potential candidate drug or supplement to control COVID-19 infection and are recommended for clinical investigation.

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Structure-based inhibitor screening of natural products against NSP15 of SARS-CoV-2 revealed thymopentin and oleuropein as potent inhibitors

Cited by 20 publications

References 50 publications

Fenolik Bileşik Oleuropein ve Hidroliz Ürünü 3-Hidroksitirozol'ün SARS-CoV-2'nin Bazı Yapısal ve Yapısal Olmayan Proteinlerine Karşı In Siliko Etkinliği

Fenolik Bileşik Oleuropein ve Hidroliz Ürünü 3-Hidroksitirozol'ün SARS-CoV-2'nin Bazı Yapısal ve Yapısal Olmayan Proteinlerine Karşı In Siliko Etkinliği

Molecular docking unveils the potential of andrographolide derivatives against COVID-19: an in silico approach

Olive Leaves as a Potential Phytotherapy in the Treatment of COVID-19 Disease; A Mini-Review

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