Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus

Odhar, Hasanain Abdulhameed

doi:10.6026/97320630016236

Cited by 81 publications

(74 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even, in blind docking, the docked conformation having the lowest binding energy depicted that dexamethasone and betamethasone have non-covalent interaction (other than H-bond interaction) with these two important amino acid residues of Mpro ( Supplementary Figure S1 ). In fact, there are many reports available in the literature where investigators noticed the formation of non-covalent bonds (other than H-bond) including alkyl bond(s) between compounds and residues of catalytic site (His41 and Cys145) of the Mpro (Bhardwaj et al, 2020 ; Das et al, 2020 ; Gurung et al, 2020 ; Islam et al, 2020 ; Joshi et al, 2020 ; Odhar et al, 2020 ). We believe that the availability and/or accessibility of Cys145 as well as His41 of Mpro may be ceased down due to the formation of alkyl bond(s) between compounds and these two residues of Mpro and such alterations possibly can inhibit its (Mpro) catalytic activity.…”

Section: Resultsmentioning

confidence: 99%

Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study

Ghosh

Chakraborty

Biswas

et al. 2020

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

The outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), represents a pandemic threat to global public health. To date, ∼530,000 people died of this disease worldwide. Presently, researchers/clinicians are adopting the drug repurposing strategy to combat this disease. It has also been observed that some repurposed anti-viral drugs may serve as potent inhibitors of SARS CoV-2 Mpro, a key component of viral replication. Apart from these anti-viral drugs, recently dexamethasone (an important corticosteroid) is effectively used to treat COVID-19 patients. However, the mechanism behind the mode of its action is not so clear. Additionally, the effect of other well-known corticosteroids to control this disease by inhibiting the proteolytic activity of Mpro is ambiguous. In this study, we have adopted computational approaches to understand these aspects. Six well-known corticosteroids (cortisone, hydrocortisone, prednisolone, methylprednisolone, betamethasone and dexamethasone) and two repurposed drugs (darunavir and lopinavir) against COVID-19 were subjected for molecular docking studies. Two of them (betamethasone and dexamethasone) were selected by comparing their binding affinities with selected repurposed drugs toward Mpro. Betamethasone and dexamethasone interacted with both the catalytic residues of Mpro (His41 and Cys145). Molecular dynamics studies further revealed that these two Mpro-corticosteroid complexes are more stable, experience less conformational fluctuations and more compact than Mpro-darunavir/lopinavir complexes. These findings were additionally validated by MM-GBSA analysis. This study provides corroboration for execution of anti-COVID-19 activity of dexamethasone. Our study also emphasizes on the use of another important corticosteroid (betamethasone) as potential therapeutic agent for COVID-19 treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study

Ghosh

Chakraborty

Biswas

et al. 2020

Journal of Biomolecular Structure and Dynamics

View full text Add to dashboard Cite

show abstract

“…Thus, the main protease of SARS-CoV-2 can represent a conserved molecular target to design a broad spectrum anti-CoV drug. (Odhar, 2020) Several options can be envisaged to control or prevent emerging infections of SARS-CoV-2. Unfortunately, no drug or vaccine has yet been approved to treat human coronaviruses.…”

Section: Introductionmentioning

confidence: 99%

“…In this field, Odhar et al used the molecular docking to screen 1615 FDA approved drugs and obtained two potential drugs (Odhar, 2020). In this work, the special attention was paid on the interaction between functional foods and the main protease of SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Virtual screening for functional foods against the main protease of SARS‐CoV‐2

et al. 2020

View full text Add to dashboard Cite

According to WHO situation report of June 30, 2020, the current epidemic outbreak of 2019 novel coronavirus (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has spread rapidly and caused a global distribution, which spreads over six continents and affects 213 countries and dependencies. This number is over 90% of the total number of regions in the world. So far, the confirmed cases of SARS-CoV-2 are 10,185,374 and the estimated mortality risk reaches ~5%. The growth rate of confirmed cases is over 1,036 times higher in last 6 months. United States of America suffers the most serious epidemic effect. The prevalence of SARS-CoV-2 in USA is over

show abstract

“…According to a full fitness score, Lymecycline and Mizolastine had more favorable binding mode, indicated by more negative fullfitness scores -1332.56 and -1300.12 kcal/mol, respectively (Table II, column 4). Azelastine can undergo an optimal binding with M pro (Odhar et al, 2020). When the clusters were analyzed it was found that N3, Indinavir, Chloroquine and Mizolastine showed that all clusters were able to fit into M pro binding pocket.…”

Section: Molecular Dockingmentioning

confidence: 99%

An in-silico evaluation of COVID-19 main protease with clinically approved drugs

Tachoua

Kabrine

Mushtaq

et al. 2020

Journal of Molecular Graphics and Modelling

View full text Add to dashboard Cite

A novel strain of coronavirus, namely, SARS-CoV-2 identified in Wuhan city of China in December 2019, continues to spread at a rapid rate worldwide. There are no specific therapies available and investigations regarding the treatment of this disease are still lacking. In order to identify a novel potent inhibitor, we performed blind docking studies on the main virus protease M pro with eight approved drugs belonging to four pharmacological classes such as: anti-malarial, anti-bacterial, anti-infective and anti-histamine. Among the eight studied compounds, Lymecycline and Mizolastine appear as potential inhibitors of this protease. When docked against M pro crystal structure, these two compounds revealed a minimum binding energy of-8.87 and-8.71 kcal/mol with 168 and 256 binding modes detected in the binding substrate pocket, respectively. Further, to study the interaction mechanism and conformational dynamics of protein-ligand complexes, Molecular dynamic simulation and MM/PBSA binding free calculations were performed. Our results showed that both Lymecycline and Mizolastine bind in the active site. And exhibited good binding affinities towards target protein. Moreover, the ADMET analysis also indicated drug-likeness properties. Thus it is suggested that the identified compounds can inhibit Chymotrypsin-like protease (3CL pro) of SARS-CoV-2.

show abstract

Molecular docking and dynamics simulation of FDA approved drugs with the main protease from 2019 novel coronavirus

Cited by 81 publications

References 32 publications

Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study

Potential therapeutic use of corticosteroids as SARS CoV-2 main protease inhibitors: a computational study

Virtual screening for functional foods against the main protease of SARS‐CoV‐2

An in-silico evaluation of COVID-19 main protease with clinically approved drugs

Contact Info

Product

Resources

About