ALL Metrics
-
Views
-
Downloads
Get PDF
Get XML
Cite
Export
Track
Research Article
Revised

Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing

[version 2; peer review: 2 approved]
PUBLISHED 11 Nov 2021
Author details Author details
OPEN PEER REVIEW
REVIEWER STATUS

This article is included in the Cheminformatics gateway.

This article is included in the Emerging Diseases and Outbreaks gateway.

This article is included in the Pathogens gateway.

This article is included in the Coronavirus (COVID-19) collection.

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus discovered that appeared in Wuhan, China, in December 2019, causes COVID-19 disease which have resulted in cases similar to SARS-atypical pneumonia. Worldwide, around 116 million cases and 2.57 million deaths are reported with new cases and increasing mortality every day. To date, there is no specific commercial treatment to control the infection. Repurpose drugs targeting the angiotensin-converting enzyme 2 (ACE2) receptor represents an alternative strategy to block the binding of SARS-CoV-2 protein S and forestall virus adhesion, internalization, and replication in the host cell.
Methods: We performed a rigid molecular docking using the receptor binding domain of the S1 subunit of S protein (RBD S1)-ACE2 (PDB ID: 6VW1) interaction site and 1,283 drugs FDA approved. The docking score, frequency of the drug in receptor site, and interactions at the binding site residues were used as analyzing criteria.
Results: This research yielded 40 drugs identified as a potential inhibitor of RBD S1-ACE2 interaction. Among the inhibitors, compounds such as ipratropium, formoterol, and fexofenadine can be found. Specialists employ these drugs as therapies to treat chronic obstructive pulmonary disease, asthma and virtually any respiratory infection.
Conclusions: Our results will serve as the basis for in vitro and in vivo studies to evaluate the potential use of those drugs to generate affordable and convenient therapies to treat COVID-19.

Keywords

COVID-19, SARS-CoV-2, ACE2, Molecular Docking, Drug Repurposing

Revised Amendments from Version 1

Edits to the manuscript focus on an improved and better organization on the abstract, methods and discussion sections, accordingly to reviewers suggestions. New references were cited on manuscript to support Introduction and Discussion sections in order to addresses the reviewers comments.

See the authors' detailed response to the review by Yogendra Nayak and Krishnaprasad Baby
See the authors' detailed response to the review by Fernando Yepes-Calderon

Introduction

Emerging viruses can be defined as those whose incidence has increased in the last twenty years or whose presence has a high probability of increasing in the near future. Diseases caused by emerging viruses are one of the biggest public health threats globally1. Some of the viruses that fall within this catalog are the avian influenza virus subtype H5N1, severe acute respiratory syndrome (SARS), Ebola, Zika, and MERS-CoV, to name a few2. Coronaviruses (CoVs) are classified into four genera, α-CoV, β-CoV, γ-CoV, and δ-CoV2. α and β infect mammals, γ birds and δ birds and mammals, respectively3. These viruses are of public health importance because they cause enteric, renal, and neurological respiratory diseases that range from asymptomatic to fatal4,5.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared in Wuhan, China, in December 2019, causing cases of SARS-like atypical pneumonia6,7, with a clinical picture of fever, general malaise, dry cough, shortness of breath and was called the coronavirus disease 2019 (COVID-19)8. It can be asymptomatic, develop mild-to-severe symptoms, or may cause death in patients with chronic diseases, such as hypertension, diabetes, and obesity9. On January 31st 2020, the World Health Organization (WHO) declared COVID-19 a public health emergency of international concern and, on March 12th, it was declared a global pandemic10. In Mexico, local transmission (phase 2 of transmission) was declared on March 24th 2020, which resulted in the suspension of non-essential activities in the country, generating economic losses in addition to public health problems and deaths associated with the disease. As of March 1st 2021, Mexico had reached 2.1 million cases of COVID-19 and 186 thousand deaths; around 116 million cases and 2.57 million deaths have been reported worldwide.

To date, there is no specific commercial treatment to control the infection1113. Measures such as early detection, blocking the route of transmission through social isolation, isolation of suspected cases, disinfection of objects, as well as frequent hand washing with soap, in addition to the use of biosafety equipment such as surgical masks for health personnel, may reduce the transmission of COVID-19 among population.

Coronaviruses, such as SARS-CoV-2, are positive-stranded RNA viruses enveloped on a membrane. The coronaviral genome is composed of approximately 30,000 nucleotides containing the envelope (E), membrane (M), spike (S), nucleocapsid (N) and ORFs, that encode non-structural proteins, including enzymes that appear during their in-host reproductive cycle-genes14.

This virus measures 70 to 100 nm and belongs to the genus β-CoV15 and it has been proposed that any of the aforementioned proteins that make up CoVs may be targets for the development of vaccines or drugs4. Protein S plays an essential role on COVID-19 infection as it mediates the internalization on host cell and for the spread of the virus in the infected host16,17. This starts when the receptor binding domain of the S1 subunit (RBDS1) of S protein binds to the peptidase domain of angiotensin-converting enzyme 2 receptor (ACE2)18 and it is know that disrupting the binding of S protein to ACE2 prevents the attaching an the later internalization of the virus to the host cell19.

This protein interaction has recently been crystallized and deposited in the Protein Data Bank database20, allowing us to use it as a model of study to test different strategies to counter SARS-CoV-2 infection, like blocking S glycoprotein-ACE2 interaction through the discovery of sites of potential pharmaceutical interest.

In 2019, Research and Development (R&D) spending in the pharmaceutical industry totaled 186 billion U.S. dollars globally and its projected to reach 233 billion U.S. dollars to 2026. Unfortunately, drug development takes large time and financial resources that not all countries possess, especially developing countries, like Mexico.

In this sense, drug repurposing or repositioning allow us to integrate all evidence, pharmacodynamics/kinetics, bioavailability, among other important parameters, from an existing and approved drug in order to manage emerging diseases, like COVID-19. All this translates into a considerable decrease in research time and investment of resources in R&D21.

Different approaches have been taken in order to disrupt SARS-CoV-2 protein S-ACE2 interaction, as an example, many works has focus on finding potential biding sites on protein S structure, however, new variant strains has been detected worldwide, like B117 in UK, P1351 in South Africa, P1 and P2 in Brazil. All variant strains display the N501Y mutation, which is located on the RBD of the S protein, making the interaction more effective. In this sense, targeting RBD may be a transitory approach, therefore, an alternative strategy would be aiming at the ACE2 receptor. Some authors have pointed out some concerns about using drugs that targeting the renin–angiotensin signaling (RAS) pathway2224, but Jia and collaborators25 highlight current efforts of exploiting ACE2 as therapeutic target, like the use of pseudo-ligands to dominate the binding site for SARS-CoV-2 as an example. Therefore, inhibition of the SARS-CoV-2 protein S-ACE2 interaction trough aiming ACE2 receptor it is a plausible strategy. In this study, we screened a library consisting of 1,283 FDA-approved drugs and acquired by Ministry of Health of Mexico in order to identify potential inhibitors of SARS-CoV-2–ACE2 interaction.

Methods

Molecular modeling, electric partial-charge assignation, ligand conformer, searching of potential binding sites, energy minimizations, visualization and docking were performed with Molecular Operating Environment package26.

Ligand preparation

The chemical structure of 1,283 drugs that comprises the updated list of reference drugs, as well as the National Compendium of Health Supplies of Mexico (June 2020 update) were obtained from the DrugBank, ZINC15 and PubChem database in September 2020. In order to simulate ligand flexibility for our rigid docking simulations, we generated a set of low-energy conformer for each drug with Conformer Import tool, with an imposed conformational cut-off energy of 3 kcal/mol from minimum energy structure of each compound, calculated with the AMBER10-EHT force field. The resulted in-house molecular data base (mdb) contain multiple conformers for each molecule and were used for rigid docking simulation.

Protein selection for ligand docking

The X-ray crystal structure of SARS-CoV-2 RBDS1 in a complex with the ACE2 (PDB ID: 6VW1, resolution of 2.68 Å) was selected as a protein target for docking simulations. Importantly, this engineered structure is the first to presents all the functionally important epitopes in the SARS-CoV-2 receptor binding motif20. Potential binding sites in ACE2 near the interface region between the SARS-CoV-2 RBDS1 and ACE2 proteins, were identified with Site Finder tool. All crystallographic water and ligands molecules were removed from the system (chains B, E, F). Hydrogen atoms (Protonate 3D tool) and partial charges (Potential Setup tool) were added to ACE2 assuming pH equal to 7.0 and using the AMBER10-EHT force field, respectively. Before docking, the ACE2 protein structure was subjected to energy minimization using the same forcefield, in order to optimize atomic contacts. Docking simulations between the optimized ACE2 structure and each of the conformers contained in the in-house database, was carried out under the rigid-docking protocol. The docking parameters were set to take each ligand conformation as unique molecule, using the Alpha Triangle algorithm as placement method (at least 100 different orientations or poses on potential binding site) and further evaluation keeping the thirty best poses accordingly the London scoring function for binding affinity with a second refinement as a Rigid Receptor using Affinity dG algorithm keeping the ten best poses. The results were analyzed by docking score, frequency of the chemical compound as a stable conformation and the types of interactions at the binding site residues.

Results

Structural analysis of SARS-CoV-2 – ACE2 interaction

The structural analysis for the SARS-CoV-2 RBDS1 of the spike protein in a complex with the ACE2 (PDB ID: 6VW1; Figure 1A) revealing a potential site for ligand binding inside ACE2 structure (Table 1). The identified receptor site (Figure 1B) is proximal to the binding site of RBDS1 with a size of 86, therefore it can be used for simulating rigid molecular docking since receptor atoms are in an exposed region of the structure, which could be in favor of drug binding.

dc649b43-62e1-421e-8d3f-073f53c93be6_figure1.gif

Figure 1. SARS-CoV-2 RBDS1interaction with human ACE2 receptor.

A) Crystallographic structure (PDB ID: 6VW1) of RBDS1(red) and ACE2 receptor (blue); B) Molecular surface of the selected binding site in ACE2.

Table 1. General characteristics of RBDS1-ACE2 receptor site.

Size.PLBHyd.SideResidues
860.842055Gln81 Tyr83 Pro84 Leu85 Gln86 Leu95 Gln98 Ala99 Gln101
Gln102 Asn103 Ala193 Asn194 His195 Tyr196
Gly205 Asp206 Tyr207 Glu208 Asn210 Arg219 Lys562

Virtual screening and molecular docking

An average of 78 conformations were generated for each ligand by Conformation Import MOE, generating 100,450 ligand conformations of the FDA approved and prescript drugs by the Mexican Public Health System.

The docking results were sorted and analyzed based on their S score, binding frequency which the drug binds to the receptor site and type of interactions, preferably, hydrogen bond, of the ligand with the selected site. We selected 38 drugs (Table 2) that presents the best docking score between −10.04 and −4.04.

Table 2. List of potential inhibitors of the RBDS1-ACE2 interaction.

Drug nameS-ScoreInteraction type (number)
Hydrogen
bond
Ionic
bond
Pi-bond
Uridine, trisodium salt-9.531030
Methotrexate sodium-10.04821
Raltritedex-8.93820
Folotyn-8.19820
CDP-choline(1-)-8.10800
Cefuroxime-8.06720
Fexofenadine-7.89700
Fludarabine phosphate-7.99601
Cefixime-9.02530
Aloin-8.16500
Domperidone-6.63510
Tamsulosin-6.62520
Cromoglycic acid-8.63401
Macitentan-8.06402
Tafluprost -Taflutan-7.94401
Thiopental(1-)-5.42400
Metoprolol-5.10400
Irinotecan-8.72301
Pitavastatin(1-)-8.40301
Amlodipine-5.94300
Verapamil-5.85310
Tolterodine-4.77300
Lopinavir-8.62200
Glimepiride-8.47210
Arformoterol-6.85200
Formoterol-6.15221
Ipratropium-5.38201
Pargeverine-4.53220
Pyrilamine-4.26210
Biperiden-4.23201
Orlistat-8.16100
Glyburide-8.10100
Ribociclib-7.96101
Ibesartan-7.17103
Cholecalciferol-5.81100
Testosterone enanthate and
estradiol valerate
-5.39100
Disopyramide phosphate-4.22102
Primaquine-4.04112

Subsequently, we shortlisted nine drugs based on their risk of teratogenicity, route of administration, interaction with other drugs, side effects and by their background as pharmacological therapy for the treatment of respiratory diseases27,28.

Fexofenadine showed interactions of hydrogen bond with Lys 74, Ala 99, Ser 105, Ser 106, Trp 203 and Asp 509 (Figure 2A) with a docking score of −7.89. Pitavastatin displays hydrogen bond interaction with Gln 102, Tyr 196, Asp 206 and pi-H stacking with Leu 73 (Figure 2B) and a docking score of −8.40. Arformoterol showed hydrogen bond interactions with Tyr 202 and Asp 206 (Figure 2C) with a docking score of −6.85. Formoterol presented hydrogen bond interactions with Gln 98, Asn 194, ionic interaction with Glu 208 and pi-H interaction with Leu 85 (Figure 2D) and presents a docking score of −6.15. Ipratropium exhibited hydrogen bond interaction with Gln 98, Gln 208 and pi-H stacking with Asp 206 (Figure 2E) and a docking score of −5.38. Pargeverine shows hydrogen bond interactions with Gln 98, Gly 205, Glu 208 and ionic interaction with Glu 208 (Figure 2F) and presents a docking score of −4.53. Cholecalciferol presented hydrogen bond interaction with Gln 102 (Figure 2G) and had a docking score of −5.81. Lopinavir displays hydrogen bond interaction with Gln 102, Tyr 196 (Figure 2H) and a docking score of −8.62. Cefixime showed hydrogen bond interaction with Gln 98, Tyr 202, Glu 208, Arg 219, Lys 562 and ionic interaction with Arg 219, Lys 562 (Figure 2I) and a docking score of −9.02.

dc649b43-62e1-421e-8d3f-073f53c93be6_figure2.gif

Figure 2. Two-dimensional representation of the interactions of the selected drugs with the ACE2 receptor binding site.

The blue arrows indicate the structural hydrogen bridge bonds, and the green arrows are the hydrogen bridge bonds with the side chain. A) Fexofenadine, B) pitavastatine, C) aformoterol, D) formoterol, E) ipatropium, F) pargeverine, G) cholecalciferol, H) lopinavir and I) cefixime.

Some pharmacokinetics characteristics27,28 of the shortlisted potential inhibitors of the RBDS1ACE2 interaction are summarized in Table 3.

Table 3. Potential inhibitors of RBDS1-ACE2 interaction selected according to desired characteristics.

DrugPharmacokineticsRoute of
administration
Drug Type/
Teratogenic risk
Bioavailability
(%)
Protein
binding (%)
MetabolismHalf-life
(hours)
Excretion
Fexofenadine30-4160-70Hepatic14.4Urine and
feces
OralAntihistaminic
(third
generation) /B
Cefixime30-5060Hepatic3-4Urine and
bile
OralAntibiotic
(Cephalosporin;
third generation)/ B
Pitavastatine6096Hepatic11FecesOralStatin /X
Lopinavir2598-99Hepatic2-3Urine and
feces
OralAntiviral -Protease
inhibitor / C
Arformoterol21-3761-64Hepatic26UrineInhaledLong lasting β
agonist/ C
Formoterol6150Hepatic17UrineInhaledLong lasting β
agonist/ C
Ipratropium20-9Gastrointestinal1.6UrineInhaledAnticholinergic
bronchodilators / B
Pargeverine8090Hepatic1.5-2UrineOral,
intravenous,
intramuscular,
rectal
Opium alkaloid
antispasmodic / D
CholecalciferolNANAHepaticNAUrineOral,
intramuscular
Vitamin

Discussion

It has been established that S protein of SARS-CoV-2 virus plays a major role during viral infection. The S protein mediates receptor recognition, cell attachment and fusion of viral membrane with host cell membrane2934. The S protein binds to ACE2 receptor through the RBDS1, mediating viral attachment to host cell35. Expression of ACE2 is ubiquitous in lung, intestine, heart and kidney, also alveolar epithelial type II cells had higher expression levels23. SARS-CoV-2, as one RNA viruses, has shown a high mutation rate as a result of lack of proofreading mechanisms, which leads to gain the ability to rapidly adapt to changes in their environment, which in turn leads to a great challenge for treating and preventing infections36. In this sense, the RBD region is a critical therapeutic target (vaccines and drugs) due to its indispensable function; however, it is suggested that mutations in this region may render pharmacological or immunological therapies ineffective37,38, therefore, it is needed to search and design alternative treatments.

In order to block this event, we propose an in silico approach to identify potential inhibitors of the SARS-CoV-2 ACE2 interaction aiming at the ACE2 receptor, blocking the virus accessibility to the membrane-bound ACE2. In this sense, Jia and collaborators25 present an extensive review for this underexplored approach to treat COVID-19, pointing that it is imperative to determine, by clinicians, the stage of the disease and comorbidities that could prove consequential for an ACE2-targeting regimen. Here, we screened a drug library consisting of 1,283 drugs, FDA approved and prescribed by the Mexican Public Health System, for potential SARS-CoV-2−ACE2 inhibitors, using a rigid receptor docking approach. Utilization of an FDA-approved drug library is an effective and ideal tool for drug repurposing in antiviral research39,40, such as zika virus41, human rhinovirus42 and hepatitis B virus43. We identify 38 potentially inhibitor drugs of SARS-CoV-2−ACE2 interaction and these are listed on Table 2. Several of those drugs were previously reported to be used for the treatment of respiratory diseases.

Within this list of potential inhibitors of the SARS-CoV-2−ACE2 interaction, is fexofenadine, a third generation antihistamine whose therapeutic indication is the treatment of symptoms of stationary allergies through the selective blockade of H1 receptors44. It possesses direct effect on combating the cytokine storm caused by SARS-CoV-2 through inhibition of histamine and interleukin-6 (IL-6) release. In silico evidence45,46 suggest that it may interact with the SARS-CoV-2 main protease enzyme MPro, a key enzyme in viral replication47, acting as a potential inhibitor.

Cefixime is a third-generation antibiotic derived from cephalosporin whose use is indicated for the treatment of infections in the upper and lower respiratory tract, otorhinolaryngological48 and urinary tract49, inhibiting the synthesis of the bacterial wall by binding to specific binding proteins for penicillin and is currently used as a secondary therapy to prevent opportunistic infections during the development of COVID-1950.

Pitavastatin is a statin indicated for lowering blood cholesterol levels by inhibiting HMG-CoA reductase, preventing cholesterol synthesis51, and it has also been observed that statin treatments can interfere with viral infectivity through inhibition of glycoprotein processing52 also, they modulates the inflammatory process at cellular level53, which is a remarkable characteristic of the SARS-CoV-2 infection. Additionally, in silico findings suggest that could be an efficient inhibitor of SARS-CoV-2 MPro54 and SARS-CoV-2 RNA-dependent RNA polymerase (RdRp)55 thru active site binding.

Lopinavir is a protease inhibitor indicated as first barrier therapy, in conjunction with Ritonavir, to treat infection caused by the HIV virus by inhibiting the HIV-1 protease56 in addition, studies in cell cultures have shown its effectiveness as an inhibitor of the replication of the MERS-CoV virus57 and SARS-CoV-158, while in severe cases of SARS-CoV-2 infection, the results of clinical trials indicate that it is not useful59.

Formoterol and aformoterol, anenantiomer of formoterol, are long-lasting selective β agonists indicated for the treatment of chronic obstructive pulmonary disease (COPD) and bronchospasms60, in the same way there is evidence of the use of these drugs as a partial inhibitor of viral replication in primary epithelial cells cultures61 and in silico data suggest their binding to the papain-like protease PLpro, a coronavirus enzyme essential for viral spread62.

Ipratropium is a bronchodilator anticholinergic indicated for the treatment of asthma, shortness of breath, cough and tightness in the chest in patients with COPD63,64. Inhalation therapy with ipratropium is currently in use to dilate bronchioles in COVID-19 patients to increase oxygen saturation levels (from <80% to 94%)65.

Pargeverine is an antispasmodic opioid alkaloid whose therapeutic indication is aimed at the treatment of painful spasms66, also, acts as anticholinergic and has a moderate and non-selective blockade of muscarinic cholinergic fibers67. Since cholinergic activity contribute to airway narrowing, this might be a potential agent to open airway obstruction.

Cholecalciferol, is a form of vitamin D (vitamin D3) that can be synthesized naturally in the skin and acts as a hormonal precursor, being converted into calcitriol, and therapeutically is used as a vitamin supplement to treat deficiencies of this vitamin68. In addition, it has been observed that vitamin D supplementation is favorable to reduce viral infections such as influenza69,70 or more aggressive cases such as HIV71 and it has recently been suggested that it also presents favorable effects before and during the infection caused by SARS-CoV-272.

Likewise, it is important to take into account that ACE2 plays an important biological role since regulates cardiovascular functions and innate immune system73 and, therefore cautions must be taken. Another point to consider is the delivery method of the drug, since the primary target must be smooth muscle, like the one surrounding the bronchioles, and lung epithelial cells in the airway and airspace compartments, hence, inhalable delivery would be the acceptable choice to deliver the drug in a selectively and localized manner.

Given these characteristics, the results obtained through our in silico approach, we consider that the aforementioned drugs are outlined as possible inhibitors of the RBDS1-ACE2 interaction. These drugs are well tolerated, commonly used and affordable, hence, most of the drugs on this list can be tested in vitro, and even in vivo and, consequently, in clinical trials for the development of adjuvant therapies to treat COVID-19.

Conclusion

In the absence of approved therapies for treatment or prevention, drug repurposing has provided fast and valuable insight into the treatment of COVID-19. Targeting ACE2 receptor as a COVID-19 therapy it is a conceivable approach since it is essential for the viral internalization. However, this approach requires an integrative evaluation of the pros and cons by a clinical context since ACE2 is a multifunctional protein. Several drugs are currently investigated by clinical trials or are already in use to treat COVID-19 patients, like lopinavir or ipratropium. In this in silico study using structure-bases virtual screening, we identified potential inhibitors of SARS-CoV-2–ACE2 by their interaction with ACE2 receptor. Based on desired characteristics like pharmacokinetics, route of administration or by their background as pharmacological therapy, we propose a shortlist of drugs suitable for testing their potential RBDS1 ACE2 inhibitory activity: fexofenadine, cefixime, pitavastatine, lopinavir, arformoterol, formoterol, ipratropium, pargeverine and cholecalciferol. Our identification of potential inhibitors of the SARS-CoV-2–ACE2 interaction among commonly use drugs highlights their potential use for treating COVID-19. Further in vitro, in vivo or clinical trial are needed to validate their potential use as inhibitors of SARS-CoV-2–ACE2 interaction.

Data availability

Source data

Protein Data Bank: Crystal structure of SARS-CoV-2 receptor binding domain (RBDS1) of the spike protein in a complex with the ACE2 receptor. https://identifiers.org/pdb:6vw1.

Ministry of Health of Mexico: Drug list used by the Ministry of Health of Mexico (June 2020 version). http://www.csg.gob.mx/Compendio/CNIS/cnis.html.

PubChem: Ligands. https://pubchem.ncbi.nlm.nih.gov74.

Drugbank: Ligands. https://go.drugbank.com75.

ZINC database: Ligands. http://zinc.docking.org76.

Extended data

Figshare: Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing, https://doi.org/10.6084/m9.figshare.1446633377

This project contains the underlying data file:

  • - Table_E1_DrugsAccessionNumber.xlsx (Accession numbers of drugs used for docking simulations)

Data is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)

Comments on this article Comments (0)

Version 2
VERSION 2 PUBLISHED 07 May 2021
Comment
Author details Author details
Competing interests
Grant information
Copyright
Download
 
Export To
metrics
Views Downloads
F1000Research - -
PubMed Central
Data from PMC are received and updated monthly.
- -
Citations
CITE
how to cite this article
Tristán-Flores FE, Casique-Aguirre D, Pliego-Arreaga R et al. Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing [version 2; peer review: 2 approved]. F1000Research 2021, 10:358 (https://doi.org/10.12688/f1000research.52168.2)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
track
receive updates on this article
Track an article to receive email alerts on any updates to this article.

Open Peer Review

Current Reviewer Status: ?
Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 2
VERSION 2
PUBLISHED 11 Nov 2021
Revised
Views
6
Cite
Reviewer Report 26 Nov 2021
Fernando Yepes-Calderon, GYM Group SA, Cali, Colombia 
Approved
VIEWS 6
No further ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Yepes-Calderon F. Reviewer Report For: Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing [version 2; peer review: 2 approved]. F1000Research 2021, 10:358 (https://doi.org/10.5256/f1000research.78910.r99909)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Views
9
Cite
Reviewer Report 22 Nov 2021
Yogendra Nayak, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India 
Approved
VIEWS 9
The revision of the manuscript by the ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Nayak Y. Reviewer Report For: Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing [version 2; peer review: 2 approved]. F1000Research 2021, 10:358 (https://doi.org/10.5256/f1000research.78910.r99910)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Version 1
VERSION 1
PUBLISHED 07 May 2021
Views
27
Cite
Reviewer Report 21 Sep 2021
Yogendra Nayak, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India 
Krishnaprasad Baby, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India 
Approved with Reservations
VIEWS 27
I am pleased to write the review for this manuscript. In this manuscript, authors have used computational tools to predict the activity of a suitable drug to treat/ prevent COVID-19. The specific target can prevent the entry of SARS-CoV-2 in ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Nayak Y and Baby K. Reviewer Report For: Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing [version 2; peer review: 2 approved]. F1000Research 2021, 10:358 (https://doi.org/10.5256/f1000research.55408.r93444)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 11 Nov 2021
    Guillermo A Silva-Martinez, Ingeniería Bioquímica, Cátedras CONACYT-Tecnologico Nacional de Mexico en Celaya, Celaya, 38010, Mexico
    11 Nov 2021
    Author Response
    We thank the reviewer for the detailed revision of our paper and for suggesting improvements.

    Abstract:
    • As the pandemic is dynamically changing the numbers, giving a country
    ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 11 Nov 2021
    Guillermo A Silva-Martinez, Ingeniería Bioquímica, Cátedras CONACYT-Tecnologico Nacional de Mexico en Celaya, Celaya, 38010, Mexico
    11 Nov 2021
    Author Response
    We thank the reviewer for the detailed revision of our paper and for suggesting improvements.

    Abstract:
    • As the pandemic is dynamically changing the numbers, giving a country
    ... Continue reading
Views
44
Cite
Reviewer Report 18 Jun 2021
Fernando Yepes-Calderon, GYM Group SA, Cali, Colombia 
Approved with Reservations
VIEWS 44
Authors use molecular docking tools to test existing medicine in their efficacy to impede the S protein-ACE2 binding and thus, disabling the entry point of Cov2 to human cells.
The authors use a solid justification to support this project. ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Yepes-Calderon F. Reviewer Report For: Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing [version 2; peer review: 2 approved]. F1000Research 2021, 10:358 (https://doi.org/10.5256/f1000research.55408.r85900)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 11 Nov 2021
    Guillermo A Silva-Martinez, Ingeniería Bioquímica, Cátedras CONACYT-Tecnologico Nacional de Mexico en Celaya, Celaya, 38010, Mexico
    11 Nov 2021
    Author Response
    We thank you for the detailed revision of our paper and for suggesting improvements. Also, we want to apologize for the long delay on our response, we were waiting for ... Continue reading
COMMENTS ON THIS REPORT
  • Author Response 11 Nov 2021
    Guillermo A Silva-Martinez, Ingeniería Bioquímica, Cátedras CONACYT-Tecnologico Nacional de Mexico en Celaya, Celaya, 38010, Mexico
    11 Nov 2021
    Author Response
    We thank you for the detailed revision of our paper and for suggesting improvements. Also, we want to apologize for the long delay on our response, we were waiting for ... Continue reading

Comments on this article Comments (0)

Version 2
VERSION 2 PUBLISHED 07 May 2021
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
Sign In
If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password.

The email address should be the one you originally registered with F1000.

Email address not valid, please try again

You registered with F1000 via Google, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Google account password, please click here.

You registered with F1000 via Facebook, so we cannot reset your password.

To sign in, please click here.

If you still need help with your Facebook account password, please click here.

Code not correct, please try again
Email us for further assistance.
Server error, please try again.