scholarly journals Structure-based assortment of herbal analogues against spike protein to restrict COVID-19 entry through hACE2 receptor: An in-silico approach

2021 ◽  
Vol 64 (2) ◽  
pp. 159-171
Author(s):  
Sourav Santra ◽  
Sasti Gopal Das ◽  
Suman Kumar Halder ◽  
Kuntal Ghosh ◽  
Amrita Banerjee ◽  
...  
Keyword(s):  
In Silico ◽  
Spike Protein ◽  
Vetiveria Zizanioides ◽  
Receptor Binding Site ◽  
Cassia Angustifolia ◽  
Global Pandemic ◽  
Therapeutic Molecules ◽  
Cymbopogon Martinii ◽  
Aconitum Heterophyllum ◽  
Justicia Adhatoda

On-going global pandemic COVID-19 has spread all over the world and has led to more than 1.97 million deaths till date. Natural compounds may be useful to protecting health in this perilous condition. Mechanism of shuttle entry of SARS-COV-2 virus is by interaction with viral spike protein with human angiotensin-converting enzyme-2 (ACE-2) receptor. To explore potential natural therapeutics, 213 important phytochemi-cals of nine medicinal plants Aconitum heterophyllum, Cassia angustifolia, Cymbopogon flexuosus, Cymbopogon martinii, Nux vomica, Phyllanthus urinaria, Swertia chirayita, Justicia adhatoda, Vetiveria zizanioides were selected for in-silico molecular docking against the spike protein of SARS-COV-2 and compared with recently prescribed drug chloroquine, ramdesivir, lopinavir and hydroxychloroquine. Results revealed that rhamnocitrin of P. urinaria, 1,5-dihydroxy-3,8-dimethoxyxanthone of S. chirayita and laevojunenol of V. zizanioides potentially binds with the receptor binding site of SARS-COV-2 spike glycoprotein and more robustly destabilized the RBD-ACE-2 binding over chloroquine, ramdesivir, lopinavir and hydroxychloroquine. It was also found that laevojunenol, rhamnocitrin, and 1,5-dihydroxy-3,8-dimethoxyxanthone qualified the criteria for drug-likeness as per Lipinski rule. After attachment of the selected phytochemical with the spike protein the affinity of the later towards ACE-2 was minimized and the effect of 1,5-dihydroxy-3,8-dimethoxyxanthone and laevojunenol was superior. Hence, rhamnocitrin of P. urinaria, 1,5-dihydroxy-3,8-dimethoxyxanthone of S. chirayita and laevojunenol of V. zizanioides, are potential therapeutic molecules for SARS-COV-2, which upon binding with spike protein changes the affinity of the spike towards ACE-2 and therefore restrict the entry of the virus into a human cell. Subsequent clinical validation is needed to confirm these phytochemicals as drugs to combat COVID-19.

scholarly journals In silico Antibody Mutagenesis for Optimizing its Binding to the Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Binquan Luan ◽  
Tien Huynh
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Drug Discovery ◽  
In Silico ◽  
Spike Protein ◽  
Computing Power ◽  
Atomic Structures ◽  
Protein Mutagenesis ◽  
Small Molecule Drugs ◽  
Global Pandemic

<p>Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic and there are currently no FDA approved medicines for treatment or prevention. Inspired by promising outcomes for convalescent plasma treatment, developing antibody drugs (biologics) to block SARS-CoV-2 infection has been the focus of drug discovery, along with tremendous efforts in repurposing small-molecule drugs. In the last several months, experimentally, many human neutralizing monoclonal antibodies (mAbs) were successfully extracted from plasma of recovered COVID-19 patients. Currently, several mAbs targeting the SARS-CoV-2's spike protein (Spro) are in clinical trials. With known atomic structures of mAb-Spro complex, it becomes possible to <i>in silico</i> investigate the molecular mechanism of mAb's binding with Spro and design more potent mAbs through protein mutagenesis studies, complementary to existing experimental efforts. Leveraging superb computing power nowadays, we propose a fully automated <i>in silico</i> protocol for quickly identifying possible mutations in a mAb (e.g.~CB6) to enhance its binding affinity with Spro for the design of more efficacious therapeutic mAbs.</p>

scholarly journals In Silico Analysis of Forskolin as a Potential Inhibitor of SARS-CoV-2

2021 ◽  
Author(s):  
Arti Kumari ◽  
Prashant Kumar ◽  
Manindra Kumar ◽  
Jainendra Kumar
Keyword(s):  
In Silico ◽  
Antiviral Agent ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Health Crisis ◽  
In Silico Docking ◽  
Protein Protein Interaction ◽  
Global Pandemic ◽  
Silico Analysis

Coronavirus disease 2019 (COVID–19) has spread rapidly as global pandemic affecting 187 countries/ regions and emerged as worldwide health crisis. Potential antiviral drugs used for the SARS -CoV-2 in clinical treatments have side effects. However, emergency vaccines are in use but despite that increase in the coronavirus cases are alarming. Thus, it is utmost need of safer antiviral agent to treat or inhibit the viral infection. Forskolin has been reported as a possible antiviral-agent. This molecule was docked with ACE2 receptor of human which is the target for the binding of S1 unit of viral S protein of SARS-CoV- 2. In silico docking was carried out on SwissDock, PatchDock and FireDock servers. The docked ACE2 structure was further docked with the RBD of the spike protein. Forskolin is able to H-bond with the hACE2 and ACE2-forskolin fails to interact with the receptor-binding domain (RBD) of the Spike protein of SARS-CoV-2. Instead, viral RBD is repulsed by the diterpene molecule through obliteration and reciprocated binding. We report first that forskolin plays a crucial role in the inhibition of protein-protein interaction of RBD and ACE2 when docked with either of the protein.

scholarly journals In silico Antibody Mutagenesis for Optimizing its Binding to the Spike Protein of SARS-CoV-2

2020 ◽  
Author(s):  
Binquan Luan ◽  
Tien Huynh
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Drug Discovery ◽  
In Silico ◽  
Spike Protein ◽  
Computing Power ◽  
Atomic Structures ◽  
Protein Mutagenesis ◽  
Small Molecule Drugs ◽  
Global Pandemic

<p>Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic and there are currently no FDA approved medicines for treatment or prevention. Inspired by promising outcomes for convalescent plasma treatment, developing antibody drugs (biologics) to block SARS-CoV-2 infection has been the focus of drug discovery, along with tremendous efforts in repurposing small-molecule drugs. In the last several months, experimentally, many human neutralizing monoclonal antibodies (mAbs) were successfully extracted from plasma of recovered COVID-19 patients. Currently, several mAbs targeting the SARS-CoV-2's spike protein (Spro) are in clinical trials. With known atomic structures of mAb-Spro complex, it becomes possible to <i>in silico</i> investigate the molecular mechanism of mAb's binding with Spro and design more potent mAbs through protein mutagenesis studies, complementary to existing experimental efforts. Leveraging superb computing power nowadays, we propose a fully automated <i>in silico</i> protocol for quickly identifying possible mutations in a mAb (e.g.~CB6) to enhance its binding affinity with Spro for the design of more efficacious therapeutic mAbs.</p>

scholarly journals Andrographis paniculata (Burm. F.) Wall. Ex Nees, Andrographolide, and Andrographolide Analogues as SARS-CoV-2 Antivirals? A Rapid Review

2021 ◽  
Vol 16 (5) ◽  
pp. 1934578X2110166
Author(s):  
Xin Yi Lim ◽  
Janice Sue Wen Chan ◽  
Terence Yew Chin Tan ◽  
Bee Ping Teh ◽  
Mohd Ridzuan Mohd Abd Razak ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
Rna Binding ◽  
Symptomatic Relief ◽  
Andrographis Paniculata ◽  
Spike Protein ◽  
Rapid Review ◽  
In Silico Studies

Drug repurposing is commonly employed in the search for potential therapeutic agents. Andrographis paniculata, a medicinal plant commonly used for symptomatic relief of the common cold, and its phytoconstituent andrographolide, have been repeatedly identified as potential antivirals against SARS-CoV-2. In light of new evidence emerging since the onset of the COVID-19 pandemic, this rapid review was conducted to identify and evaluate the current SARS-CoV-2 antiviral evidence for A. paniculata, andrographolide, and andrographolide analogs. A systematic search and screen strategy of electronic databases and gray literature was undertaken to identify relevant primary articles. One target-based in vitro study reported the 3CLpro inhibitory activity of andrographolide as being no better than disulfiram. Another Vero cell-based study reported potential SARS-CoV-2 inhibitory activity for both andrographolide and A. paniculata extract. Eleven in silico studies predicted the binding of andrographolide and its analogs to several key antiviral targets of SARS-CoV-2 including the spike protein-ACE-2 receptor complex, spike protein, ACE-2 receptor, RdRp, 3CLpro, PLpro, and N-protein RNA-binding domain. In conclusion, in silico and in vitro studies collectively suggest multi-pathway targeting SARS-CoV-2 antiviral properties of andrographolide and its analogs, but in vivo data are needed to support these predictions.

scholarly journals In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis

2021 ◽  
pp. 100969
Author(s):  
Azza H. Harisna ◽  
Rizky Nurdiansyah ◽  
Putri H. Syaifie ◽  
Dwi W. Nugroho ◽  
Kurniawan E. Saputro ◽  
...  
Keyword(s):  
In Silico ◽  
Spike Protein ◽  
Main Protease ◽  
Potential Inhibitors

scholarly journals In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2–Spike RBD Interface

2021 ◽  
Vol 22 (4) ◽  
pp. 1695
Author(s):  
Bruno O. Villoutreix ◽  
Vincent Calvez ◽  
Anne-Geneviève Marcelin ◽  
Abdel-Majid Khatib
Keyword(s):  
Amino Acid ◽  
South African ◽  
In Silico ◽  
Neutralizing Antibodies ◽  
Viral Escape ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
The South ◽  
African Strain ◽  
The Uk

SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells. It has been reported that the UK and South African strains may have higher transmission capabilities, eventually in part due to amino acid substitutions on the SARS-CoV-2 Spike protein. The pathogenicity seems modified but is still under investigation. Here we used the experimental structure of the Spike RBD domain co-crystallized with part of the ACE2 receptor, several in silico methods and numerous experimental data reported recently to analyze the possible impacts of three amino acid replacements (Spike K417N, E484K, N501Y) with regard to ACE2 binding. We found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable. It is unclear if the N501Y substitution in the South African strain could counterbalance the K417N and E484K Spike replacements with regard to ACE2 binding. Our finding suggests that the UK strain should have higher affinity toward ACE2 and therefore likely increased transmissibility and possibly pathogenicity. If indeed the South African strain has a high transmission level, this could be due to the N501Y replacement and/or to substitutions in regions located outside the direct Spike–ACE2 interface but not so much to the K417N and E484K replacements. Yet, it should be noted that amino acid changes at Spike position 484 can lead to viral escape from neutralizing antibodies. Further, these amino acid substitutions do not seem to induce major structural changes in this region of the Spike protein. This structure–function study allows us to rationalize some observations made for the UK strain but raises questions for the South African strain.

scholarly journals Current Therapeutic Molecules and Targets in Neurodegenerative Diseases Based on in silico Drug Design

2018 ◽  
Vol 16 (6) ◽  
pp. 649-663 ◽  
Author(s):  
Sheikh Arslan Sehgal ◽  
Mirza A. Hammad ◽  
Rana Adnan Tahir ◽  
Hafiza Nisha Akram ◽  
Faheem Ahmad
Keyword(s):  
Drug Design ◽  
Neurodegenerative Diseases ◽  
In Silico ◽  
In Silico Drug Design ◽  
Therapeutic Molecules
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