In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

Bank, Sarbashri; Basak, Nipa; Girish, GV; De, Sujit Kumar; Maiti, Smarajit

doi:10.21203/rs.3.rs-30401/v1

Cited by 4 publications

(6 citation statements)

References 52 publications

(69 reference statements)

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“…The review showed Curcumin-derived polyphenols exhibit antiviral activity for influenza, hepatitis C virus, HIV, anti-inflammatory, antibacterial, and antioxidant properties and also exert substantial anticarcinogenic activities (Heger et al, 2013;Nelson et al, 2017;Praditya et al, 2019b). Wet lab experimental approaches for the study of interactions between therapeutic substance and target proteins are not cheap, not safe, labors, and time-consuming (Basak et al, 2020;Bachmann & Lewis, 2005). There are many alternative methods are available for solving these problems.…”

Section: Discussionmentioning

confidence: 99%

The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

Mulu

Gajaa

Woldekidan

et al. 2021

PeerJ

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The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. As part of this, silico were studied to discover and introduce COVID-19 antiviral drugs and results showed that protease inhibitors could be very effective in controlling. This study aims to investigate the binding affinity of three curcumin derived polyphenols against COVID-19 the main protease (Mpro), binding pocket, and identification of important residues for interaction. In this study, molecular modeling, auto-dock coupled with molecular dynamics simulations were performed to analyze the conformational, and stability of COVID-19 binding pocket with diferuloylmethane, demethoxycurcumin, and bisdemethoxycurcumin. All three compounds have shown binding affinity −39, −89 and −169.7, respectively. Demethoxycurcumin and bisdemethoxycurcumin showed an optimum binding affinity with target molecule and these could be one of potential ligands for COVID-19 therapy. And also, COVID-19 main protease binding pocket binds with the interface region by one hydrogen bond. Moreover, the MD simulation parameters indicated that demethoxycurcumin and bisdemethoxycurcumin were stable during the simulation run. These findings can be used as a baseline to develop therapeutics with curcumin derived polyphenols against COVID-19.

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Section: Discussionmentioning

confidence: 99%

The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

Mulu

Gajaa

Woldekidan

et al. 2021

PeerJ

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“…In this study, CBD was the most potent out of five phyto-cannabinoids (cannabidiol, cannabidiolic acid, delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinolic acid, cannabinol), and even more potent than the reference drugs lopinavir, chloroquine and remdesivir. Intriguingly, CBD may be able to bind also to the spike protein as has been demonstrated in a recent in silico study [8]. A further peptide possibly playing more than just one role in early infection is apelin.…”

Section: Preclinical Data Suggest a Potential Benefit Of Cannabidiol mentioning

confidence: 76%

Experimental Studies and First Retrospective Clinical Data Suggest a Possible Benefit of CBD in COVID-19

2021

J Pharmacol Pharm Res

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SARS-CoV-2 damages human cells and organs by multiple mechanisms. Intriguingly, preclinical studies have demonstrated that cannabidiol (CBD) may interact in many ways with virus entry and cell stress on one hand, and with inflammatory mechanisms affecting the lung and other organs on the other. A number of very recent in vitro and in silico studies demonstrate that CBD may be able to affect a high number of different proteins that are involved in the infection process, among them the Glucose Regulated Protein 78, heme oxygenase 1 (HO1), the virus-specific protease SARS-CoV-2 Mpro and apelin. Furthermore, a number of animal studies confirmed independently the anti-inflammatory and organ protective properties of CBD. As there is still no optimal treatment known, highly purified magisterial phyto-CBD has been included to a standard therapy for COVID-19 as an adjunct anti-inflammatory drug. A retrospective analysis of data of 30 patients hospitalised for COVID-19 and who received adjuvant low dose CBD (up to 300 mg/day), show a more pronounced reduction of virus load, normalisation of lymphocyte counts and of other abnormal laboratory parameters when compared to a non-matched group of patients who did not receive CBD.

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“…It is concluded that grazoprevir could be the most potent inhibitor of spike glycoprotein, as several studies are focusing on the efficiency of blocking spike by glycoprotein (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ). Other therapeutics such as ivermectin (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ), ledipasvir, teniposide, velpatasvir (Chen Y. W. et al, 2020 ; Kadioglu et al, 2020 ), and rifabutin (Bank et al, 2020 ; Kadioglu et al, 2020 ) also showed potential inhibitory action against the spike glycoprotein of SARS-CoV-2. Among the suggested candidate drugs of spike protein, 17 drug molecules were repurposed for COVID-19 and approved by the FDA (Home, 2013 ).…”

Section: In Silico Medicinesmentioning

confidence: 99%

“…Isothymol has been suggested against human ACE2 for the treatment of COVID-19, although wet lab investigation is yet to be started (Abdelli et al, 2020 ). Moreover, it has been found that HCQ has the maximum capacity to act on multiple drug targets, namely, Mpro, spike protein, RNA-dependent RNA polymerase, interleukin (IL) 6, IL2, IL10, and interferon alpha 1 (IFNA1) (Bank et al, 2020 ; Elfiky, 2020 ; Kim and Kim, 2020 ; Srivastava et al, 2020 ). Few other drug molecules were found to be effective against multiple drug targets.…”

Section: In Silico Medicinesmentioning

confidence: 99%

“…For examples, nelfinavir showed efficacy against Mpro and nucleocapsid protein (Chandel et al, 2020 ; Mittal et al, 2020 ; Mothay and Ramesh, 2020 ; Musarrat et al, 2020 ), whereas ivermectin was found to have potential against spike protein and 2′-o-ribose-methyltransferase (Chaudhary and Mishra, 2016 ; Mothay and Ramesh, 2020 ; Sharun et al, 2020 ). Grazoprevir reportedly exhibits inhibitory action against both spike protein and Mpro (Ibrahim et al, 2020 ; Kadioglu et al, 2020 ; Mohamed et al, 2020 ; Shah et al, 2020 ), whereas rifabutin was suggested against spike protein and nucleocapsid of SARS-CoV-2 (Bank et al, 2020 ; Kadioglu et al, 2020 ). About 215 clinical trial projects are ongoing in different phases on HCQ for the treatment of COVID-19 and studies leading to mixed conclusions for those candidate drugs (Gautret et al, 2020 ; Yazdany and Kim, 2020 ).…”

Section: In Silico Medicinesmentioning

confidence: 99%

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A Revisit to the Research Updates of Drugs, Vaccines, and Bioinformatics Approaches in Combating COVID-19 Pandemic

Sumon

Hussain

Hasan

et al. 2021

Front. Mol. Biosci.

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A new strain of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the coronavirus disease 2019 (COVID-19) pandemic was first detected in the city of Wuhan in Hubei province, China in late December 2019. To date, more than 1 million deaths and nearly 57 million confirmed cases have been recorded across 220 countries due to COVID-19, which is the greatest threat to global public health in our time. Although SARS-CoV-2 is genetically similar to other coronaviruses, i.e., SARS and Middle East respiratory syndrome coronavirus (MERS-CoV), no confirmed therapeutics are yet available against COVID-19, and governments, scientists, and pharmaceutical companies worldwide are working together in search for effective drugs and vaccines. Repurposing of relevant therapies, developing vaccines, and using bioinformatics to identify potential drug targets are strongly in focus to combat COVID-19. This review deals with the pathogenesis of COVID-19 and its clinical symptoms in humans including the most recent updates on candidate drugs and vaccines. Potential drugs (remdesivir, hydroxychloroquine, azithromycin, dexamethasone) and vaccines [mRNA-1273; measles, mumps and rubella (MMR), bacille Calmette-Guérin (BCG)] in human clinical trials are discussed with their composition, dosage, mode of action, and possible release dates according to the trial register of US National Library of Medicines (clinicaltrials.gov), European Union (clinicaltrialsregister.eu), and Chinese Clinical Trial Registry (chictr.org.cn) website. Moreover, recent reports on in silico approaches like molecular docking, molecular dynamics simulations, network-based identification, and homology modeling are included, toward repurposing strategies for the use of already approved drugs against newly emerged pathogens. Limitations of effectiveness, side effects, and safety issues of each approach are also highlighted. This review should be useful for the researchers working to find out an effective strategy for defeating SARS-CoV-2.

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In-silico analysis of potential interaction of drugs and the SARS-CoV-2 spike protein

Cited by 4 publications

References 52 publications

The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

Experimental Studies and First Retrospective Clinical Data Suggest a Possible Benefit of CBD in COVID-19

A Revisit to the Research Updates of Drugs, Vaccines, and Bioinformatics Approaches in Combating COVID-19 Pandemic

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