Targeting virus–host interaction by novel pyrimidine derivative: an<i>in silico</i>approach towards discovery of potential drug against COVID-19

Mishra

Journal of Biomolecular Structure and Dynamics

et al. 2020

Like common cold and flu, SARC-CoV-2 virus spreads by droplets of sneezes or coughs which virus affects people of various age groups. Today, this virus is almost distributed all over the world. Since binding process plays a crucial role between host and receptor, therefore, we studied the molecules intended toward inhibition process through molecular docking and molecular dynamics simulation process. From the molecular docking study, it is noteworthy that remdesivir shows better binding affinity toward the main protease of SARS-CoV2 compared to other studied drugs. Within studied phytochemicals, carnosic acid shows better binding poses toward main protease of SARS-CoV2 among studied phytochemicals. The amino acid residues GLN110 and PHE294 were almost found in all the studied interactions of drugs and phytochemicals with main protease of SARS-CoV-2. Furthermore, the results show a larger contribution of the Van der Waals energies as compared to others like electrostatic energies suggesting that ligands at the binding pocket are predominantly stabilized by hydrophobic interactions. The conformational change during ligand binding was predicted from Gibbs free energy landscape analysis through molecular dynamics simulation. We observed that, there were two main free energy basins for both docked carnosic acid complex and for docked remdesivir complex, only one main free energy basin was found in the global free energy minimum region.

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

“…The conformational change during ligand binding was predicted by comparison the Gibbs free energy landscape analysis for PC1 and PC2 (Das et al, 2020;Rane et al, 2020). The free energy landscape was monitored by using gmx_sham utility of Gromacs module.…”

Section: Molecular Dynamic Simulationmentioning

confidence: 99%

Molecular dynamics simulation perception study of the binding affinity performance for main protease of SARS-CoV-2

Mishra

Journal of Biomolecular Structure and Dynamics

et al. 2020

Journal of Biomolecular Structure and Dynamics

“…In that direction, immense efforts are also being made towards the discovery of effective therapeutic agents which could successfully bind with the different drug targets such as the spike (S) protein, enzymes such as proteases, viral RNA etc. and inhibit different steps of the infection (Akaji & Konno, 2020 ; Coelho et al, 2020 ; Preeti et al, 2020 ; Rane et al, 2020 ; Zhao et al, 2021 ; Zhu et al, 2020 ). For examples the spike (S) protein of SARS-CoV-2 interacts with different receptors such as angiotensin-converting enzyme 2 (ACE-2), TM protease serine 2 (TMPRSS-2) etc.…”

Section: Introductionmentioning

confidence: 99%

In silico identification and validation of triarylchromones as potential inhibitor against main protease of severe acute respiratory syndrome coronavirus 2

Chandel

Tripathi

Nayar

et al. 2021

Self Cite

The ongoing pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 has emerged as a severe threat to the life of human kind. The identification and designing of appropriate and reliable drug molecule for the treatment of COVID-19 patients is the pressing need of the present time. Among different drug targets, the main protease of SARS-CoV-2 is being considered as most effective target. In addition to the drug repurposing, different compounds of natural as well as synthetic origins are being investigated for their efficacy against different drug targets of SARS-CoV-2 virus. In that context, the chromone based natural flavonols have also exhibited significant antiviral properties against different targets of SARS-CoV-2. The in silico studies presented here discloses the efficacy of triarylchromones (TAC) as potential inhibitor against main protease of SARS-CoV-2. The molecular docking and ADMET study performed using 14 arylchromones which could easily be accessed through simple synthetic protocols, revealed best binding affinities in case of TAC-3 (–11.2 kcal/mol), TAC-4 (–10.5 kcal/mol), TAC-6 (–11.2 kcal/mol), TAC-7 (–10.0 kcal/mol). Additional validation studies including molecular dynamics simulation and binding energy calculation using MMGBSA for protein ligand complex for 100 ns revealed the best binding interaction of TAC-3, TAC-4, TAC-6, TAC-7 against main protease of SARS-CoV-2. Moreover, the in vitro and preclinical validation of identified compounds will help us to understand the molecular mechanisms of regulation of TACs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

“…The spike protein present on the surface of SARS-CoV-2 facilitates the entry of virus particles through the human angiotensin-converting enzyme 2 (hACE2) receptors binding domain [ 20 ] and is proteolytic activated by host cell proteases [ 19 ]. Therefore, several research groups are trying to decipher the interaction of hACE2 and spike protein as a novel drug target site to stop the pathogenicity [ 5 , 21 ]. The hACE2 receptors present on the lungs, arteries, heart, kidneys and small intestine, colon, thymus, bone marrow, lymph nodes, the brain of the host cells [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…The hACE2 receptors present on the lungs, arteries, heart, kidneys and small intestine, colon, thymus, bone marrow, lymph nodes, the brain of the host cells [ 22 ]. The S1 subunit of the spike protein binds to the receptor-binding domain and assists the attachment of spike protein to the receptor, resulting in conformational changes into the spike protein [ 21 ]. TMPRSS211, a serine protease and lysosomal proteases cathepsins produced by the host cell cleaves the spike protein at the boundary of S1/S2 in such a way that S1 dissociates from the complex [ 19 ] and intense structural change in S2 domain was observed, which is necessary for the fusion of the virus into the host cell membrane [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Nucleic acid-based therapy for coronavirus disease 2019

Piyush¹,

Rajarshi²,

Chatterjee³

et al. 2020

Heliyon

Self Cite

The coronavirus disease 2019 (COVID-19), the pandemic that originated in China has already spread into more than 190 countries, resulting in huge loss of human life and many more are at the stake of losing it; if not intervened with the best therapeutics to contain the disease. For that aspect, various scientific groups are continuously involved in the development of an effective line of treatment to control the novel coronavirus from spreading rapidly. Worldwide scientists are evaluating various biomolecules and synthetic inhibitors against COVID-19; where the nucleic acid-based molecules may be considered as potential drug candidates. These molecules have been proved potentially effective against SARS-CoV, which shares high sequence similarity with SARS-CoV-2. Recent advancements in nucleic acid-based therapeutics are helpful in targeted drug delivery, safely and effectively. The use of nucleic acid-based molecules also known to regulate the level of gene expression inside the target cells. This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2.