Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach

Hasan, Mahmudul; Parvez, Sorwer Alam; Azim, Kazi Faizul; Imran, Abdus Shukur; Raihan, Topu; Gulshan, Airin; Muhit, Samuel; Akhand, Rubaiat Nazneen; Ahmed, Syed Sayeem Uddin; Uddin, Bashir

doi:10.1016/j.biopha.2021.111742

Cited by 16 publications

(14 citation statements)

References 108 publications

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“…From the docking results, the interactions of M pro with the peptide GSRY and that with the inhibitor N3 were overlapped at residues HIS163, GlY143, GLU166, GLN189 and MET165; and GlY143, GLU166, GLN189 and MET165 were the critical residues for the successful binding of M pro SARS-CoV-2 ( Hasan et al, 2021 ). Thus, the peptide GSRY may be developed as a novel coronavirus inhibitor.…”

Section: Resultsmentioning

confidence: 99%

“…In the absence of treatment drugs, COVID-19 spreads faster than previous coronaviruses (SARS-CoV and MERS-CoV) ( Heymann & Shindo, 2020 ). In response to this occurrence, on January 2020, the World Health Organization's Emergency Committee on International Health Regulations declared COVID-19 as a “public health emergency” ( Hasan et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there is no specific clinical treatment for SARS-CoV-2-mediated infections ( Hasan et al, 2021 ). One possible drug target is the major structural protein of the virus, and the development of drugs targeting this protein has been suggested ( Zhou, Hou, Shen, Huang, & Martin, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Zhao

et al. 2022

LWT

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COVID-19 is a global health emergency that causes serious concerns. A global effort is underway to identify drugs for the treatment of COVID-19. One possible solution to the present problem is to develop drugs that can inhibit SARS-CoV-2 main protease (M pro ), a coronavirus protein that been considered as one among many drug targets. In this work, lactoferrin from Bos taurus L. was in silico hydrolyzed. The bioactivity, water solubility, and ADMET properties of the generated peptides were predicted using various online tools. The molecular interactions between M pro and the peptides were studied using molecular docking and molecular dynamic simulation. The results demonstrated that peptide GSRY was predicted to have better physicochemical properties, and the value of ‘-C DOCKER interaction energy’ between peptide GSRY and M pro was 80.8505 kcal/mol. The interaction between the peptide GSRY and the native ligand N3 co-crystallized with M pro had overlapped amino acids, i.e., HIS163, GlY143, GLU166, GLN189 and MET165. Molecular dynamic simulation revealed that M pro /GSRY complexes were stable. Collectively, the peptide GSRY may be a potential candidate drug against M pro of SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Zhao

et al. 2022

LWT

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“…The frequent mutations that occurred in this virus also make it more challenging to develop therapeutics [112]. Even those having organized health systems, every country is facing difficulties to end COVID-19 [113]. The newly emerged Omicron variant of SARS-CoV-2 can infect vaccinated people and thus has increased the risk of SARS-CoV-2 reinfection [114].…”

Section: Sars-cov-2mentioning

confidence: 99%

Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

Parvez

Ohtsuki

2022

Brain Sciences

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The cerebellum governs motor coordination and motor learning. Infection with external microorganisms, such as viruses, bacteria, and fungi, induces the release and production of inflammatory mediators, which drive acute cerebellar inflammation. The clinical observation of acute cerebellitis is associated with the emergence of cerebellar ataxia. In our animal model of the acute inflammation of the cerebellar cortex, animals did not show any ataxia but hyperexcitability in the cerebellar cortex and depression-like behaviors. In contrast, animal models with neurodegeneration of the cerebellar Purkinje cells and hypoexcitability of the neurons show cerebellar ataxia. The suppression of the Ca2+-activated K+ channels in vivo is associated with a type of ataxia. Therefore, there is a gap in our interpretation between the very early phase of cerebellar inflammation and the emergence of cerebellar ataxia. In this review, we discuss the hypothesized scenario concerning the emergence of cerebellar ataxia. First, compared with genetically induced cerebellar ataxias, we introduce infection and inflammation in the cerebellum via aberrant immunity and glial responses. Especially, we focus on infections with cytomegalovirus, influenza virus, dengue virus, and SARS-CoV-2, potential relevance to mitochondrial DNA, and autoimmunity in infection. Second, we review neurophysiological modulation (intrinsic excitability, excitatory, and inhibitory synaptic transmission) by inflammatory mediators and aberrant immunity. Next, we discuss the cerebellar circuit dysfunction (presumably, via maintaining the homeostatic property). Lastly, we propose the mechanism of the cerebellar ataxia and possible treatments for the ataxia in the cerebellar inflammation.

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“…In order to determine the drug surface hotspot of Lyn tyrosine kinase protein (PDB ID: 3A4O), the lyn and its inhibitor complex structure were analysed by, Discovery Studio, and PyMOL [30] The molecular docking analysis was carried out to study the binding pattern of Bosutinib, Baicalein, Myricetin and Quercetin inhibitor the Lyn protein of Breast cancer, and the results allowed us to do comparative structural analysis of screened the natural Lyn inhibitors [31].…”

Section: Structural Insights Regarding Drug Surface Hotspots In Lyn Proteinmentioning

confidence: 99%

Virtual Screening through Molecular Docking Analysis to Identify Potential Natural Inhibitor(s) of Lyn Tyrosine Kinase- An In-silico Approach

Kulavi

Banerjee

Sengupta

et al. 2021

JPRI

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Breast cancer on becoming one of the leading cancer types, emerged as an important barrier in increasing life expectancy of the overall population. In the current study, some compounds were screened based on literature survey for the identification of natural bioactive compounds as potential inhibitors of Lyn tyrosine kinase. Therefore, a multi-step molecular docking was carried out using AutoDock embedded in the MGL Tools. After initial screening, molecules having a higher docking score and binding free energy compared to Tamoxifen were considered for further assessment. Some already known synthetic lyn tyrosine kinase inhibitor have been used for better understanding of the comparative study. Based on in silico Lipinski filter analysis, toxicity prediction, pharmacokinetic analysis, four compounds were proposed to be promising inhibitors of Lyn tyrosine kinase. Furthermore, the binding interactions of all proposed inhibitors of Lyn showed strong ligand efficiency in terms of energy score obtained with the help of molecular modelling analyses. Hence, the proposed compounds out of which three are bioactive compounds might be taken forward as potential next-generation Lyn kinase inhibitors for managing Lyn associated breast cancer after experimental authentication.

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Main protease inhibitors and drug surface hotspots for the treatment of COVID-19: A drug repurposing and molecular docking approach

Cited by 16 publications

References 108 publications

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Identification of lactoferrin-derived peptides as potential inhibitors against the main protease of SARS-CoV-2

Acute Cerebellar Inflammation and Related Ataxia: Mechanisms and Pathophysiology

Virtual Screening through Molecular Docking Analysis to Identify Potential Natural Inhibitor(s) of Lyn Tyrosine Kinase- An In-silico Approach

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