The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2

Shagufta,; Ahmad, Irshad

doi:10.1016/j.ejmech.2021.113157

Cited by 38 publications

(36 citation statements)

References 137 publications

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“…Due to its RdRp inhibitory properties, it is considered for clinical trial against SARS‐CoV‐2. [34] The synthesized agents revealing variable anti‐SARS‐CoV‐2 properties were considered for molecular modeling (Discovery Studio 2.5 software, standard CDOCKER technique, PDB: 7CTT) for validating the bio‐observations. [35]…”

Section: Resultsmentioning

confidence: 99%

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

et al. 2021

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Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). We have developed a set of pyrazine‐based small molecules. A series of pyrazine conjugates was synthesized by microwave‐assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR‐CoV‐2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine‐triazole conjugates ( 5 d – g ) and ( S )‐N‐(1‐(benzo[d]thiazol‐2‐yl)‐2‐phenylethyl)pyrazine‐2‐carboxamide 12 i show significant potency against SARS‐CoV‐2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).

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Section: Resultsmentioning

confidence: 99%

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

et al. 2021

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“…The binding energy of the hit molecules ( 2 - 22 ) have been compared with the co-crystallized ligand remdesivir ( 1 , Table 1 , Entry 1). Further, these hits ( 2 - 22 ) have been found with better binding energy as compared to other promising RdRp inhibitors such as ribavirin ( 23 ), penciclovir ( 24 ), favipravir ( 25 ), [36] molnupiravir ( 26 ) and sofosbuvir ( 27 ) [37] . Total twenty-one identified macrocyclic hits have been found to possess binding energy lesser than -12.5 Kcal/mol and presented in Table 1 and their 2D-possess with the formed interactions have been presented in Figure S1-S4 (see supporting informartion).…”

Section: Resultsmentioning

confidence: 99%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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“…Therefore, the binding site of spike protein inhibitors may modulate Renin-Angiotensin System-associated side effects. 45 , 46 , 47 …”

Section: Discussionmentioning

confidence: 99%

Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay

Chen

Pan

et al. 2022

Journal of Traditional and Complementary Medicine

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Background and aim Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. Methods The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. Results and conclusion We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico . In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant ( K d ) = 0.468 μM, 1.712 μM, 6.650 μM, 2.86 μM, 3.761 μM and 4.27 μM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50–90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC 50 > 100 μM; dioscin and celastrol showed IC 50 = 1.5625 μM and 0.9866 μM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. Section: 1. Natural Products. Taxonomy (classification by evise) SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study .

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The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2

Cited by 38 publications

References 137 publications

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Potential natural products that target the SARS-CoV-2 spike protein identified by structure-based virtual screening, isothermal titration calorimetry and lentivirus particles pseudotyped (Vpp) infection assay

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