A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules

Kumar, Devendra; Chauhan, Gaurav; Kalra, Sourav; Kumar, Bhupinder; Gill, Manjinder Singh

doi:10.1016/j.bioorg.2020.104326

Cited by 21 publications

(16 citation statements)

References 130 publications

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“…Different software tested the interaction between the tested compounds and the binding site through physics-based equations used to calculate their binding affinities (Sliwoski et al, 2014 ). SARS-CoV-2 proteins, particularly proteases and spike proteins (Prajapat et al, 2020 ), have been targeted in many docking investigations hoping to understand the key amino acids essential for the interactions at the active site in SARS-CoV-2 (Calligari et al, 2020 ; Dahab et al, 2020 ; Khan et al, 2020 ; Kumar et al, 2020 ; Mohammad et al, 2020 ; Wu et al, 2020 ; Jairajpuri et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

et al. 2021

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The rapid and global spread of a new human coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Here, we consider drug repurposing as an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. We review current information concerning the global health issue of COVID-19 including promising approved drugs, e.g., human angiotensin-converting enzyme inhibitors (hACEIs). Besides, we describe computational approaches to be used in drug repurposing and highlight examples of in-silico studies of drug development efforts against SARS-CoV-2. Alacepril and lisinopril were found to interact with human angiotensin-converting enzyme 2 (hACE2), the host entranceway for SARS-CoV-2 spike protein, through exhibiting the most acceptable rmsd_refine values and the best binding affinity through forming a strong hydrogen bond with Asn90, which is assumed to be essential for the activity, as well as significant extra interactions with other receptor-binding residues. Furthermore, molecular dynamics (MD) simulations followed by calculation of the binding free energy were also carried out for the most promising two ligand-pocket complexes from docking studies (alacepril and lisinopril) to clarify some information on their thermodynamic and dynamic properties and confirm the docking results as well. These results we obtained probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiments and accurate clinical trials are needed to confirm the potential preventive and treatment effect of these compounds.

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Section: Introductionmentioning

confidence: 99%

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

et al. 2021

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“…SARS CoV-2 (COVID-19) is a newly emerged pandemic triggered by the severe acute respiratory syndrome coronavirus-2 that created an unprecedented global health crisis [ 1 ]. It is a zoonotic virus with more highly contagious properties than the Middle East respiratory syndrome virus (MERS CoV) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is a zoonotic virus with more highly contagious properties than the Middle East respiratory syndrome virus (MERS CoV) [ 2 ]. SARS CoV-2 is of the Coronaviridae family that causes acute respiratory disease, which could be lethal, with an approximate 10.2% mortality rate [ 1 , 2 ]. The disease can cause death due to severe alveolar destruction and hemorrhage, as well as progressive respiratory failure [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

et al. 2021

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Since the emergence of the SARS-CoV-2 pandemic in 2019, it has remained a significant global threat, especially with the newly evolved variants. Despite the presence of different COVID-19 vaccines, the discovery of proper antiviral therapeutics is an urgent necessity. Nature is considered as a historical trove for drug discovery, especially in global crises. During our efforts to discover potential anti-SARS CoV-2 natural therapeutics, screening our in-house natural products and plant crude extracts library led to the identification of C. benedictus extract as a promising candidate. To find out the main chemical constituents responsible for the extract’s antiviral activity, we utilized recently reported SARS CoV-2 structural information in comprehensive in silico investigations (e.g., ensemble docking and physics-based molecular modeling). As a result, we constructed protein–protein and protein–compound interaction networks that suggest cnicin as the most promising anti-SARS CoV-2 hit that might inhibit viral multi-targets. The subsequent in vitro validation confirmed that cnicin could impede the viral replication of SARS CoV-2 in a dose-dependent manner, with an IC50 value of 1.18 µg/mL. Furthermore, drug-like property calculations strongly recommended cnicin for further in vivo and clinical experiments. The present investigation highlighted natural products as crucial and readily available sources for developing antiviral therapeutics. Additionally, it revealed the key contributions of bioinformatics and computer-aided modeling tools in accelerating the discovery rate of potential therapeutics, particularly in emergency times like the current COVID-19 pandemic.

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“…[14][15][16][17][18] The recognition of the co-crystallized structure with inhibitor N3 (PDB 6LU7) interaction with human ACE2 (PDB 6M0J) provides a grasp of the active sites and the important amino acids that are responsible for the restraint of SARS-CoV-2. 19 Moreover, it is having a precious role in enzymatic activity leading to its posttranslational modication of replicase polyproteins.…”

Section: Introductionmentioning

confidence: 99%

In silico study of natural compounds from sesame against COVID-19 by targeting M^pro, PL^pro and RdRp

et al. 2021

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A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules

Abstract: Graphical abstract

Cited by 21 publications

References 130 publications

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

In silico study of natural compounds from sesame against COVID-19 by targeting M^pro, PL^pro and RdRp

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A perspective on potential target proteins of COVID-19: Comparison with SARS-CoV for designing new small molecules

Abstract: Graphical abstract

Cited by 21 publications

References 130 publications

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Molecular Docking and Dynamics Simulation Revealed the Potential Inhibitory Activity of ACEIs Against SARS-CoV-2 Targeting the hACE2 Receptor

Cnicin as an Anti-SARS-CoV-2: An Integrated In Silico and In Vitro Approach for the Rapid Identification of Potential COVID-19 Therapeutics

In silico study of natural compounds from sesame against COVID-19 by targeting Mpro, PLpro and RdRp

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Product

Resources

About

In silico study of natural compounds from sesame against COVID-19 by targeting M^pro, PL^pro and RdRp