Peptide modelling and screening against human ACE2 and spike glycoprotein RBD of SARS-CoV-2

Rathod, Shravan B.; Prajapati, Pravin B; Punjabi, Lata B; Prajapati, Kuntal N; Chauhan, Neha; Mansuri, Mohmedyasin F.

doi:10.1007/s40203-020-00055-w

Cited by 21 publications

(21 citation statements)

References 48 publications

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“…Most of previous contributions investigated the docking of small molecules to RBD focusing on the interface with ACE2 (Rathod et al. 2020 ), but the presence of other sites also emerged (Alexpandi et al. 2020 ; Basu et al.…”

Section: Resultsmentioning

confidence: 99%

Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

Ribaudo

Coghi

Yang

et al. 2021

Natural Product Research

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The mechanism of host cell invasion of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 is connected with the interaction of spike protein (S) with angiotensin-converting enzyme 2 (ACE2) through receptor-binding domain (RBD). Small molecules targeting this assembly are being investigated as drug candidates to contrast SARS-CoV-2. In this context, chloroquine, an antimalarial agent proposed as a repurposed drug to treat coronavirus disease-19 (COVID-19), was hypothesized to bind RBD among its other mechanisms. Similarly, artemisinin and its derivatives are being studied as potential antiviral agents. In this work, we investigated the interaction of artemisinin, its metabolite dihydroartemisinin and chloroquine with RBD by means of computational tools and in vitro . Docking studies showed that the compounds interfere with the same region of the protein and molecular dynamics (MD) simulations demonstrated the stability of the predicted complexes. Bio-layer interferometry showed that chloroquine dose-dependently binds RBD (KD = 35.9 µM) more efficiently than artemisinins.

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Section: Resultsmentioning

confidence: 99%

Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

Ribaudo

Coghi

Yang

et al. 2021

Natural Product Research

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“…Many other drugs and compounds, such as monoclonal antibodies, TCMs [ 35 ], and antiviral peptides [ 36 ], were screened. Our group experimentally screened ACE2 binding components from antipsychotics [ 37 ], histamine H 1 receptor antagonists [ 38 ], and glucocorticoid drugs [ 39 ] with ACE2/CMC model.…”

Section: Resultsmentioning

confidence: 99%

Screening and evaluation of anti-SARS-CoV-2 components from Ephedra sinica by ACE2/CMC-HPLC-IT-TOF-MS approach

Wang

Liang

et al. 2021

Anal Bioanal Chem

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Graphical abstract Traditional Chinese medicines played an important role in the treatment of COVID-19 in 2020. Ephedra sinica , one of the major constituent herbs of multi-component herbal formula, has been widely used to treat COVID-19 in China. However, its active components are still unclear. The objectives of this study are to screen and evaluate active components from the traditional Chinese medicine Ephedra sinica for the treatment of COVID-19. In our study, we established an ACE2/CMC bioaffinity chromatography model, and then developed an ACE2/CMC-HPLC-IT-TOF-MS system for the active compounds screening and identification from Ephedra sinica extract. We performed molecular docking and surface plasmon resonance (SPR) assays to assess the binding characteristics (binding mode and K D value). We used CCK-8 staining to assess the toxicity of screened compounds, and also used SARS-CoV-2 pseudovirus to observe the viropexis effect of screened compounds in ACE2 h cells. In this current work, one fraction was fished out, separated and identified as ephedrine (EP), pseudoephedrine (PEP), and methylephedrine (MEP). Binding assays showed that the three compounds could bind with ACE2 in a special way to some amino acid residues, similar to the way SARS-CoV-2 bound with ACE2. Additionally, the three compounds, especially EP, can inhibit the entrance of SARS-CoV-2 spike pseudovirus into ACE2 h cells because they can reduce the entrance ratio of pseudovirus in the pseudovirus model. Overall, the ACE2/CMC-HPLC-IT-TOF-MS system was established and verified to be suitable for ACE2-targeted bioactive compound screening. EP, PEP, and MEP with ACE2-binding features were screened out from Ephedra sinica , and acted as blockers inhibiting SARS-CoV-2 spike pseudovirus entering ACE2 h cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00216-021-03233-7.

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“…Elmezayen and coworkers [ 8 ] evaluated interactions between these residues and the ligands analyzed. The work of Tariq and coworkers [ 15 ] had RBD as one of the targets and interaction with 2 of the 5 amino acid residues of the active site already described has been reported (Gly496 and Try505), showing no interactions of the ligands analyzed with the Ans487, Glu37, Arg393 residues [ 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

The pulmonary route as a way to drug repositioning in COVID-19 therapy

Sarcinelli

Silva

et al. 2021

Journal of Drug Delivery Science and Technology

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Introduction The outbreak of the disease caused by the new coronavirus (COVID-19) has been affecting society’s routine and its patterns of interaction worldwide, in addition to the impact on the global economy. To date, there is still no clinically effective treatment for this comorbidity, and drug repositioning might be a good strategy considering the established clinical safety profile. In this context, since COVID-19 affects the respiratory tract, a promising approach would be the pulmonary drug delivery. Objective Identify repurposing drug candidates for the treatment of COVID-19 based on the data of ongoing clinical trials and in silico studies and also assess their potential to be applied in formulations for pulmonary administration. Method A narrative literature review was conducted between June and July 2020, by extracting the results from Clinical Trials, PubMed, Web of Science and Science Direct databases. Results By crossing the results obtained from diverse sources, 21 common drugs were found, from which only 4 drugs presented studies of pulmonary release formulations, demonstrating the need for greater investment and incentive in this field. Conclusion Even though the lung is a target that facilitates viral infection and replication, formulations for pulmonary delivery of suitable drugs are still lacking for COVID-19 treatment. However, it is indisputable that the pandemic constitutes a concrete demand, with a profound impact on public health, and that, with the appropriate investments, it will give the pharmaceutical industry an opportunity to reinforce the pulmonary delivery field.

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Peptide modelling and screening against human ACE2 and spike glycoprotein RBD of SARS-CoV-2

Cited by 21 publications

References 48 publications

Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

Computational and experimental insights on the interaction of artemisinin, dihydroartemisinin and chloroquine with SARS-CoV-2 spike protein receptor-binding domain (RBD)

Screening and evaluation of anti-SARS-CoV-2 components from Ephedra sinica by ACE2/CMC-HPLC-IT-TOF-MS approach

The pulmonary route as a way to drug repositioning in COVID-19 therapy

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