Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease

Marinho, Emanuelle Machado; Neto, João Batista de Andrade; Silva, Jacilene; Silva, Cecília Rocha da; Cavalcanti, Bruno C.; Marinho, Emmanuel Silva; Júnior, Hélio Vitoriano Nobre

doi:10.1016/j.micpath.2020.104365

Cited by 124 publications

(64 citation statements)

References 31 publications

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“…Nitrogen of cyano group of remdesivir forms additional hydrogen bonding with Gln127 and Glu290 amino acid residues. Hydrogen bonds and their amounts play an important role in determining the molecular's interaction, identification and stability with the pharmacological receptor 19 . Although various residues also contributed through strong hydrophobic interactions, were not shown in the binding pose.…”

Section: Discussionmentioning

confidence: 99%

Computational studies of drugs for possible action against Covid-19 infections

Mishra

Panigrahi²

2020

J. Drug Delivery Ther.

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SARS-Cov-2 has emerged highly contagious viral infections so far and posed a global threat with significant human casualties and severe economic losses. There is urgent demand to develop rational therapies to control the drastic spread of the virus. Although there is no specific regimens are available to combat this pandemic situation so far. An attempt was made to perform Insilco studies of drugs applicable to respiratory tract infections with crucial SARS-COV-2 main protease (M-pro) enzyme. Insilco docking study was performed with Molegro Virtual Docker 5.5 on number of available medications of different categories specified for respiratory tract infections.Result indicates that Azithromycin, Dexamethasone and Remdesivir are highly effective and mainly interacted with key amino acid residues with hydrogen bonds and displayed excellent docking score -133, -141 and -153 kcal/mole respectively. This study advocates the possible use Azithromycin, Dexamethasone and Remdesivir drugs in combination to battle this pandemic condition. Further, this study will provide rationalized drugs and target for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections. Keywords: Viruses, SARS-COV-2, Covid-19, Drugs, Computational docking Studies, Drug Design

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Section: Discussionmentioning

confidence: 99%

Computational studies of drugs for possible action against Covid-19 infections

Mishra

Panigrahi²

2020

J. Drug Delivery Ther.

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“…The in silico binding analyses are becoming a hot area of scientific investigation, especially in the post COVID-19 era, for screening drugs (Ancy et al, 2020;Khan et al, 2020;Kumar et al, 2020;Marinho et al, 2020), synthetic compounds (Niu et al, 2008;Sepay et al, 2020;Ton et al, 2020;Wang et al, 2017) and natural products (Ghosh et al, 2020;Gupta et al, 2020;Gurung et al, 2020;Joshi et al, 2020;Narkhede et al, 2020) to measure the potential of these compounds for binding with the SARS-CoV-2 main protease. In the field of computer-aided drug designing (CADD), primarily used for the identification of a lead compound, the molecular docking analyses have been enormously employed for mapping and delineating the atomic level details of binding interaction between ligand and the receptor.…”

Section: Computational Studiesmentioning

confidence: 99%

Synthetic flavonoids as potential antiviral agents against SARS-CoV-2 main protease

Batool

Mughal

Zia

et al. 2020

Journal of Biomolecular Structure and Dynamics

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The COVID-19 pandemic has claimed more than a million lives worldwide within a short time span. Due to the unavailability of specific antiviral drugs or vaccine, the infections are causing panic both in general public and among healthcare providers. Therefore, an urgent discovery and development of effective antiviral drug for the treatment of COVID-19 is highly desired. Targeting the main protease (M pro) of the causative agent, SARS-CoV-2 has great potential for drug discovery and drug repurposing efforts. Published crystal structures of SARS-CoV-2 M pro further facilitated in silico investigations for discovering new inhibitors against M pro. The present study aimed to screen several libraries of synthetic flavonoids and benzisothiazolinones as potential SARS-CoV-2 M pro inhibitors using in silico methods. The short-listed compounds after virtual screening were filtered through SwissADME modeling tool to remove molecules with unfavorable pharmacokinetics and medicinal properties. The drug-like molecules were further subjected to iterative docking for the identification of top binders of SARS-CoV-2 M pro. Finally, molecular dynamic (MD) simulations and binding free energy calculations were performed for the evaluation of the dynamic behavior, stability of protein-ligand complex, and binding affinity, resulting in the identification of thioflavonol, TF-9 as a potential inhibitor of M pro. The computational studies further revealed the binding of TF-9 close to catalytic dyad and interactions with conserved residues in the S1 subsite of the substrate binding site. Our in-silico study demonstrated that synthetic analogs of flavonoids, particularly thioflavonols, have a strong tendency to inhibit the main protease M pro , and thereby inhibit the reproduction of SARS-CoV-2.

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“…Protein Data Bank (PDB) provided about 110 protein structures that were linked with SARS-CoV2 for better insight of structural binding sites of virus that provide a basis for rational drug targeting [10]. From Virtual Screening the scientists had found some new anti-viral drugs through Molecular Docking [11]. It is an important approach in the repurposing of the drug which was performed by analyzing the targeted protein catalytic site and finding the drug molecules that bind with it.…”

Section: Introductionmentioning

confidence: 99%

Virtual Screening of Inhibitory Agents Against SARS-CoV2

Pervez¹,

Bilal²,

Khan³

et al. 2021

Preprint

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<div>Severe Acute Respiratory Syndrome (SARS-CoV2) infected about 93 million people and killed over two million worldwide. The disease transmits very quickly, therefore; due to its severity and widespread the World Health Organization has declared this menace as ‘Global Pandemic’. An urgent need was felt to manage this disease through aggressive and efficient research process all over the globe. That’s why drug re-purposing of 212 chemical entities (CEs) against SARS-COV2 was found to be one of the efficient ways in finding new indications of already discovered drugs amisdst of the discovery of a new drug. Results of this study revealed that out of 212 CEs, only Etodolac forms a hydrogen (H)-bond with a relatively low energy and active central fragment, demonstrating more significant interaction with SARS-CoV2 viral proteins. Other CEs exhibit good pharmacokinetics properties with the least acute toxicity through ADMET analysis. We also discovered other therapeutic applications of these CEs through Molinspiration. Etodolac, a non-steroidal anti-inflammatory drug forms H-bonding with 5.6 kcal/mol binding energy with active residues of this receptor. This drug created H-bonding with PHE326 and PRO328, with pyridine group, and was found more suitable to control SARS-CoV2.</div>

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Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease

Cited by 124 publications

References 31 publications

Computational studies of drugs for possible action against Covid-19 infections

Computational studies of drugs for possible action against Covid-19 infections

Synthetic flavonoids as potential antiviral agents against SARS-CoV-2 main protease

Virtual Screening of Inhibitory Agents Against SARS-CoV2

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