scholarly journals Current Trends in SPR Biosensing of SARS-CoV-2 Entry Inhibitors

Chemosensors ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 330
Author(s):  
Elba Mauriz ◽  
Laura M. Lechuga

The emerging risk of viral diseases has triggered the search for preventive and therapeutic agents. Since the beginning of the COVID-19 pandemic, greater efforts have been devoted to investigating virus entry mechanisms into host cells. The feasibility of plasmonic sensing technologies for screening interactions of small molecules in real time, while providing the pharmacokinetic drug profiling of potential antiviral compounds, offers an advantageous approach over other biophysical methods. This review summarizes recent advancements in the drug discovery process of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) inhibitors using Surface Plasmon Resonance (SPR) biosensors. A variety of SPR assay formats are discussed according to the binding kinetics and drug efficacies of both natural products and repurposed drugs. Special attention has been given to the targeting of antiviral agents that block the receptor binding domain of the spike protein (RBD-S) and the main protease (3CLpro) of SARS-CoV-2. The functionality of plasmonic biosensors for high-throughput screening of entry virus inhibitors was also reviewed taking into account experimental parameters (binding affinities, selectivity, stability), potential limitations and future applications.

2020 ◽  
Vol 25 (10) ◽  
pp. 1141-1151 ◽  
Author(s):  
Wei Zhu ◽  
Catherine Z. Chen ◽  
Kirill Gorshkov ◽  
Miao Xu ◽  
Donald C. Lo ◽  
...  

COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gangan Yan ◽  
Dongsheng Li ◽  
Yuan Lin ◽  
Zhenghao Fu ◽  
Haiyan Qi ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible and has caused a pandemic named coronavirus disease 2019 (COVID-19), which has quickly spread worldwide. Although several therapeutic agents have been evaluated or approved for the treatment of COVID-19 patients, efficacious antiviral agents are still lacking. An attractive therapeutic target for SARS-CoV-2 is the main protease (Mpro), as this highly conserved enzyme plays a key role in viral polyprotein processing and genomic RNA replication. Therefore, the identification of efficacious antiviral agents against SARS-CoV-2 Mpro using a rapid, miniaturized and economical high-throughput screening (HTS) assay is of the highest importance at the present. Results In this study, we first combined the fluorescence polarization (FP) technique with biotin-avidin system (BAS) to develop a novel and step-by-step sandwich-like FP screening assay to quickly identify SARS-CoV-2 Mpro inhibitors from a natural product library. Using this screening assay, dieckol, a natural phlorotannin component extracted from a Chinese traditional medicine Ecklonia cava, was identified as a novel competitive inhibitor against SARS-CoV-2 Mpro in vitro with an IC50 value of 4.5 ± 0.4 µM. Additionally, dieckol exhibited a high affinity with SARS-CoV-2 Mpro using surface plasmon resonance (SPR) analysis and could bind to the catalytic sites of Mpro through hydrogen-bond interactions in the predicted docking model. Conclusions This innovative sandwich-like FP screening assay enables the rapid discovery of antiviral agents targeting viral proteases, and dieckol will be an excellent lead compound for generating more potent and selective antiviral agents targeting SARS-CoV-2 Mpro.


2021 ◽  
Vol 33 (11) ◽  
pp. 2599-2607
Author(s):  
Ruchika Yogesh ◽  
Noopur Srivastava

Viruses use the host cell’s biochemical machinery for replication and survival; and also undergo mutations to evade the immune response and achieve better transmission. These features make it challenging to develop selective drugs to kill viruses only and not the host cells. New and effective pharmaceutical agents are required to overcome this challenge. Tetrazole moiety, as a bio-isostere of carboxylic acid/amide group, has been extensively used as a potent pharmacophore in several bioactivities. Intrigued by the necessity of finding new antiviral compounds and tendency of tetrazole scaffolds to render various bioactivity profiles, this review article comprising literature reports of tetrazole-based synthetic compounds with promising antiviral activity is presented. This review comprises significant literature reports from the scientific databases published during the past four decades. It is found that tetrazole based molecules are promising endeavor for the development of potential agents against influenza virus, HIV, HCV and other viruses.


mBio ◽  
2021 ◽  
Author(s):  
Yongzhen Liu ◽  
Chao Qin ◽  
Youliang Rao ◽  
Chau Ngo ◽  
Joshua J. Feng ◽  
...  

The ongoing COVID-19 pandemic is caused by SARS-CoV-2, which is rapidly evolving with better transmissibility. Understanding the molecular basis of the SARS-CoV-2 interaction with host cells is of paramount significance, and development of antiviral agents provides new avenues to prevent and treat COVID-19 diseases. This study describes a molecular characterization of innate immune evasion mediated by the SARS-CoV-2 Nsp5 main protease and subsequent development of a small-molecule inhibitor.


2020 ◽  
Author(s):  
Levent Çavaş ◽  
Cengizhan Dag ◽  
Miguel Carmena-Barreño ◽  
Carlos Martínez-Cortés ◽  
José Pedro Cerón-Carrasco ◽  
...  

<p>SARS-CoV-2 has been exhibiting extremely spreading property all around the world since its existence from Wuhan-China in December-2019. Although it has caused a death toll of over than 1.3 M people, no validated vaccine has been proposed yet. On the other hand, very dense studies on the vaccine development have been carrying out in some countries such as the US, Germany, UK, China and Russia. Due to side effects of current antiviral agents used in the therapy of COVID-19, there is a great need for the development of alternative compounds for this disease. Caulerpin (CPN) and caulerpenyne (CYN), predominant natural secondary metabolites from invasive marine green algae <i>Caulerpa cylindracea,</i>are proposed to neutralize the virus from two targets: spike protein (5XLR) and main protease (6YB7) in this study. The results show that the binding energies related to CPN-6YB7 and CYN-6YB7 interactions are found to be -8.02 kcal/mol and -6.83 kcal/mol, respectively. The binding energies were -9.68 kcal/mol and -7.53 kcal/mol, respectively, for CPN-5XLR and CYN-5XLR. In the molecular dynamics results, RMSD values show that CPN and CYN can form stable complexes with the proteins where CYN is more stable with 6YB7 and CPN interacts better with 5XLR. These differences seem to be based on the type of interactions of the complexes. In conclusion, caulerpin and caulerpenyne can further be investigated experimentally for their anti-SARS-CoV-2 efficiency. </p>


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yan Li ◽  
Jinyong Zhang ◽  
Zilei Duan ◽  
Ning Wang ◽  
Xiangcheng Sun ◽  
...  

2020 ◽  
Author(s):  
Levent Çavaş ◽  
Cengizhan Dag ◽  
Miguel Carmena-Bargueño ◽  
Carlos Martínez-Cortés ◽  
José Pedro Cerón-Carrasco ◽  
...  

<p>SARS-CoV-2 has been exhibiting extremely spreading property all around the world since its existence from Wuhan-China in December-2019. Although it has caused a death toll of over than 1.3 M people, no validated vaccine has been proposed yet. On the other hand, very dense studies on the vaccine development have been carrying out in some countries such as the US, Germany, UK, China and Russia. Due to side effects of current antiviral agents used in the therapy of COVID-19, there is a great need for the development of alternative compounds for this disease. Caulerpin (CPN) and caulerpenyne (CYN), predominant natural secondary metabolites from invasive marine green algae <i>Caulerpa cylindracea,</i>are proposed to neutralize the virus from two targets: spike protein (5XLR) and main protease (6YB7) in this study. The results show that the binding energies related to CPN-6YB7 and CYN-6YB7 interactions are found to be -8.02 kcal/mol and -6.83 kcal/mol, respectively. The binding energies were -9.68 kcal/mol and -7.53 kcal/mol, respectively, for CPN-5XLR and CYN-5XLR. In the molecular dynamics results, RMSD values show that CPN and CYN can form stable complexes with the proteins where CYN is more stable with 6YB7 and CPN interacts better with 5XLR. These differences seem to be based on the type of interactions of the complexes. In conclusion, caulerpin and caulerpenyne can further be investigated experimentally for their anti-SARS-CoV-2 efficiency. </p>


2020 ◽  
Author(s):  
Mostafa ◽  
Mohammed ◽  
Hatem

Abstract Total 40 natural compounds were selected to perform the molecular docking studies to screen and identify the potent antiviral agents specifically for Severe Acute Respiratory Syndrome Coronavirus 2 that causes coronavirus disease 2019 (COVID-19). The key targets of COVID-19, protease (PDB ID: 6M0K, 6Y2F and 7BQY) and RNA polymerase (PDB ID: 7bV2) were used to dock our target compounds by Molecular Operating Environment (MOE) version 2014.09. After an extensive screening analysis, 20 compounds exhibit good binding affinities to one or more of the COVID-19 targets. 7 out of 20 compounds were predicted to overcome the activity of the 4 drug targets. The top 7 hits are compounds; Flacourticin (3), Sagerinic acid (16), Hordatine A (23), Hordatine B (24), N-feruloyl tyramine dimer (25), Bisavenanthramides B-5 (29) and Vulnibactins (40). According to our results, all these top hits was found to have a better binding scores than Remdesivir, the native ligand in RNA polymerase target (PDB ID: 7bV2). Hordatines are phenolic compounds present in barley, were found to exhibit the highest binding affinity to both protease and polymerase through forming strong hydrogen bonds with the catalytic residues, as well as significant interactions with other receptor-binding residues. These results probably provided an excellent lead candidate for the development of therapeutic drugs against COVID-19. Eventually, animal experiment and accurate clinical trials are needed to confirm the preventive potentials of these compounds.


2020 ◽  
Author(s):  
Roopa Guthappa

<p><b>SARS CoV-2 a pandemic influenza like infectious disease emerged in December 2019 has spread throughout the world within few months. Scientists are trying their best to find medicine and vaccine. Usnic acid and its derivatives as herbal supplements are widely used as mouth wash, cosmetics, antiviral agents. In this study, usnic acid and its derivative-sodium usnate in comparison with favipiravir are docked with main protease and spike protein RBD </b><b>6M0J of SARS Cov-2. Usnic acid and sodium usnate exhibit better binding affinities for main protease and spike RBD. The data has been compared with favipiravir. Favipiravir, usnic acid, sodium usnate shows binding affinity of -4.25, -8.05 and -8.55 kcal/mol respectively with main protease. While favipiravir, usnic acid and sodium usnate exhibit binding affinities of -4.25, -6.02 and -6.53 kcal/mol with spike RBD respectively. One of the interesting features is that the inhibition constant values of usnic acid is 1.27 µM and sodium usnate is 539.86 nM in comparison to favipiravir (764.13 µM) with main protease. </b></p>


2020 ◽  
Author(s):  
Roopa Guthappa

<p><b>SARS CoV-2 a pandemic influenza like infectious disease emerged in December 2019 has spread throughout the world within few months. Scientists are trying their best to find medicine and vaccine. Usnic acid and its derivatives as herbal supplements are widely used as mouth wash, cosmetics, antiviral agents. In this study, usnic acid and its derivative-sodium usnate in comparison with favipiravir are docked with main protease and spike protein RBD </b><b>6M0J of SARS Cov-2. Usnic acid and sodium usnate exhibit better binding affinities for main protease and spike RBD. The data has been compared with favipiravir. Favipiravir, usnic acid, sodium usnate shows binding affinity of -4.25, -8.05 and -8.55 kcal/mol respectively with main protease. While favipiravir, usnic acid and sodium usnate exhibit binding affinities of -4.25, -6.02 and -6.53 kcal/mol with spike RBD respectively. One of the interesting features is that the inhibition constant values of usnic acid is 1.27 µM and sodium usnate is 539.86 nM in comparison to favipiravir (764.13 µM) with main protease. </b></p>


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