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.

In Silico Analysis of Plant-Derived Medicinal Compounds Against Spike Protein of SARS-CoV-2 and Ace2

2021 ◽  
pp. 299-313
Author(s):  
Tanya Sharma ◽  
Mohammad Nawaid Zaman ◽  
Shazia Rashid ◽  
Seneha Santoshi
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Medicinal Compounds ◽  
Silico Analysis

scholarly journals Perspectives of a myosin motor activator agent with increased selectivity

2018 ◽  
Vol 96 (7) ◽  
pp. 676-680
Author(s):  
Péter Nánási ◽  
István Komáromi ◽  
János Almássy
Keyword(s):  
In Silico ◽  
Clinical Performance ◽  
Ryanodine Receptors ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Cardiac Myosin ◽  
In Silico Docking ◽  
Myosin Motor ◽  
Omecamtiv Mecarbil ◽  
Silico Analysis

Clinical treatment of heart failure is still not fully solved. A novel class of agents, the myosin motor activators, acts directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. Omecamtiv mecarbil, the lead molecule of this group, is now in human phase 3 displaying promising clinical performance. However, omecamtiv mecarbil is not selective to myosin, because it readily binds to and activates cardiac ryanodine receptors (RyR-2), an effect that may cause complications in case of overdose. In this study, in silico analysis was performed to investigate the docking of omecamtiv mecarbil and other structural analogues to cardiac myosin heavy chain and RyR-2 to select the structure that has a higher selectivity to myosin over RyR-2. In silico docking studies revealed that omecamtiv mecarbil has comparable affinity to myosin and RyR-2: the respective Kd values are 0.60 and 0.87 μmol/L. Another compound, CK-1032100, has much lower affinity to RyR-2 than omecamtiv mecarbil, while it still has a moderate affinity to myosin. It was concluded that further research starting from the chemical structure of CK-1032100 may result a better myosin activator burdened probably less by the RyR-2 binding side effect. It also is possible, however, that the selectivity of omecamtiv mecarbil to myosin over RyR-2 cannot be substantially improved, because similar moieties seem to be responsible for the high affinity to both myosin and RyR-2.

scholarly journals Structural Dissection of Viral Spike-Protein Binding of SARS-CoV-2 and SARS-CoV-1 to the Human Angiotensin-Converting Enzyme 2 (ACE2) as Cellular Receptor

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1038
Author(s):  
Deborah Giordano ◽  
Luigi De Masi ◽  
Maria Antonia Argenio ◽  
Angelo Facchiano
Keyword(s):  
Angiotensin Converting Enzyme ◽  
In Silico Analysis ◽  
Host Cells ◽  
Spike Protein ◽  
Cellular Receptor ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
The World ◽  
Silico Analysis

An outbreak by a new severe acute respiratory syndrome betacoronavirus (SARS-CoV-2) has spread CoronaVirus Disease 2019 (COVID-19) all over the world. Immediately, following studies have confirmed the human Angiotensin-Converting Enzyme 2 (ACE2) as a cellular receptor of viral Spike-Protein (Sp) that mediates the CoV-2 invasion into the pulmonary host cells. Here, we compared the molecular interactions of the viral Sp from previous SARS-CoV-1 of 2002 and SARS-CoV-2 with the host ACE2 protein by in silico analysis of the available experimental structures of Sp-ACE2 complexes. The K417 amino acid residue, located in the region of Sp Receptor-Binding Domain (RBD) of the new coronavirus SARS-CoV-2, showed to have a key role for the binding to the ACE2 N-terminal region. The R426 residue of SARS-CoV-1 Sp-RBD also plays a key role, although by interacting with the central region of the ACE2 sequence. Therefore, our study evidenced peculiarities in the interactions of the two Sp-ACE2 complexes. Our outcomes were consistent with previously reported mutagenesis studies on SARS-CoV-1 and support the idea that a new and different RBD was acquired by SARS-CoV-2. These results have interesting implications and suggest further investigations.

In Silico Analysis of Active Compounds from Siddha Herbal Infusion of Ammaiyar Koondhal Kudineer (Akk) Against SARS-CoV-2 Spike Protein and Its ACE2 Receptor Complex

2020 ◽  
Author(s):  
Rajamaheswari Krishnasamy ◽  
Anand T ◽  
Mursaleen Baba ◽  
Muthu Vijai Bharath ◽  
Jamyang Phuntsho ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Receptor Complex ◽  
Active Compounds ◽  
Silico Analysis

scholarly journals In Silico Analysis of Honeybee Venom Protein Interaction with Wild Type and Mutant (A82V + P375S) Ebola Virus Spike Protein

Biologics ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 45-55
Author(s):  
Muhammad Muzammal ◽  
Muzammil Ahmad Khan ◽  
Mohammed Al Mohaini ◽  
Abdulkhaliq J. Alsalman ◽  
Maitham A. Al Hawaj ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Strong Interaction ◽  
In Silico ◽  
Ebola Virus ◽  
In Silico Analysis ◽  
Spike Protein ◽  
Honeybee Venom ◽  
Silico Analysis ◽  
Venom Proteins ◽  
Proteins And Peptides

Venom from different organisms was used in ancient times to treat a wide range of diseases, and to combat a variety of enveloped and non-enveloped viruses. The aim of this in silico research was to investigate the impact of honeybee venom proteins and peptides against Ebola virus. In the current in silico study, different online and offline tools were used. RaptorX (protein 3D modeling) and PatchDock (protein–protein docking) were used as online tools, while Chimera and LigPlot + v2.1 were used for visualizing protein–protein interactions. We screened nine venom proteins and peptides against the normal Ebola virus spike protein and found that melittin, MCD and phospholipase A2 showed a strong interaction. We then screened these peptides and proteins against mutated strains of Ebola virus and found that the enzyme phospholipase A2 showed a strong interaction. According to the findings, phospholipase A2 found in honeybee venom may be an effective source of antiviral therapy against the deadly Ebola virus. Although the antiviral potency of phospholipase A2 has been recorded previously, this is the first in silico analysis of honeybee phospholipase A2 against the Ebola viral spike protein and its more lethal mutant strain.

scholarly journals Sea Urchin Pigments as Potential Therapeutic Agents Against the Spike Protein of SARS-CoV-2 Based on in Silico Analysis

2020 ◽  
Author(s):  
Elena Susana Barbieri ◽  
Tamara Rubilar ◽  
Ayelén Gázquez ◽  
Marisa Avaro ◽  
Erina Noé Seiler ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
In Silico Analysis ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Therapeutic Drug ◽  
The Novel ◽  
Novel Coronavirus ◽  
Silico Analysis

Several studies have been published regarding the interaction between the spike protein of the novel coronavirus SARS-CoV-2 and ACE2 receptor in the host cells. In the presente work, we evaluated the in silico properties of two sea urchin pigments, Echinochrome A (EchA) and Spinochromes (SpinA) against the Spike protein (S) towards finding a potential therapeutic drug against the disease caused by the novel coronavirus (COVID-19). The best ensemble docking pose of EchaA and SpinA showed a binding affinity of -5.9 and -6.7 kcal mol-1, respectively. The linked aminoacids (T505, G496 and Y449 for EchA and Y449, Q493 and G496 for SpinA) are in positions involved in ACE2 binding in both RBDs frim SARS-CoV and SARS-CoV-2 suggesting that EchA and SpinA may interact with Spike proteins drom both viruses. The results suggest that these pigments could act as inhibitors of S protein, pointing them as antiviral drugs for SARS-CoV-2.<br>

scholarly journals An in silico analysis of early SARS-CoV-2 variant B.1.1.529 (Omicron) genomic sequences and their epidemiological correlates

2021 ◽  
Author(s):  
Ashutosh Kumar ◽  
Adil Asghar ◽  
Himanshu N. Singh ◽  
Muneeb A. Faiq ◽  
Sujeet Kumar ◽  
...  
Keyword(s):  
In Silico ◽  
Immune Escape ◽  
Mutational Analysis ◽  
In Silico Analysis ◽  
Spike Protein ◽  
World Health ◽  
Genomic Sequences ◽  
Binding Motif ◽  
New Variant ◽  
Silico Analysis

Background: A newly emerged SARS-CoV-2 variant B.1.1.529 has worried health policymakers worldwide due to the presence of a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) has designated it as a global variant of concern (VOC) and has named as Omicron. A surge in new COVID-19 cases has been reported from certain geographical locations, primarily in South Africa (SA) following the emergence of Omicron. Materials and methods: We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID (until 2021-12-6) to predict the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the current epidemiological data (new COVID-19 cases and deaths) from SA to understand whether the Omicron has an epidemiological advantage over existing variants. Results: Compared to the current list of global VOCs/VOIs (as per WHO) Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with Alpha variant for the complete sequence as well as for RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There has been a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%), on the contrary, the incidences of new deaths have not been increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58). Conclusions: Omicron may have greater immune escape ability than the existing VOCs/VOIs. However, there are no clear indications coming out from the predictive mutational analysis that the Omicron may have higher virulence/lethality than other variants, including Delta. The higher ability for immune escape may be a likely reason for the recent surge in Omicron cases in SA.

scholarly journals Are the SARS-CoV-2 Variants Greater Threats? - An In Silico Analysis of the Spike Protein

2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Wilson J ◽  
◽  
Sokolova V ◽  
Ji H F ◽  
◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Binding Affinities ◽  
S Protein ◽  
Preventative Measures ◽  
Global Pandemic ◽  
Production And Distribution ◽  
In Silico Molecular Docking ◽  
Silico Analysis

March 2020 marked the beginning of a global pandemic caused by SARSCoV- 2. With the development, production and distribution of several vaccines there are hopes to an end in sight. However, with the emergence of several mutated viral strains concerns are mounting as to the effectiveness of the current treatments and preventative measures against the new strains. Herein we analyzed and compared the interaction of the SARS-CoV-2 Spike (S) protein and its variants with human Angiotensin Converting Enzyme (ACE-2) and the binding affinities of several possible S-protein inhibitors with these variants via in silico molecular docking studies. The binding affinities of all the variants to ACE- 2 are less than that of SARS-CoV-2, indicating they are less potent than SARSCoV- 2. The inhibitors, however, showed decreased binding affinity to most of the mutant S-proteins than SARS-CoV-2, indicating it is more difficult to treat COVID using the therapeutic approach targeting the S-protein.

scholarly journals Sea Urchin Pigments as Potential Therapeutic Agents Against the Spike Protein of SARS-CoV-2 Based on in Silico Analysis

2020 ◽  
Author(s):  
Elena Susana Barbieri ◽  
Tamara Rubilar ◽  
Ayelén Gázquez ◽  
Marisa Avaro ◽  
Erina Noé Seiler ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
In Silico Analysis ◽  
Protein S ◽  
Host Cells ◽  
Spike Protein ◽  
Therapeutic Drug ◽  
The Novel ◽  
Novel Coronavirus ◽  
Silico Analysis

Several studies have been published regarding the interaction between the spike protein of the novel coronavirus SARS-CoV-2 and ACE2 receptor in the host cells. In the presente work, we evaluated the in silico properties of two sea urchin pigments, Echinochrome A (EchA) and Spinochromes (SpinA) against the Spike protein (S) towards finding a potential therapeutic drug against the disease caused by the novel coronavirus (COVID-19). The best ensemble docking pose of EchaA and SpinA showed a binding affinity of -5.9 and -6.7 kcal mol-1, respectively. The linked aminoacids (T505, G496 and Y449 for EchA and Y449, Q493 and G496 for SpinA) are in positions involved in ACE2 binding in both RBDs frim SARS-CoV and SARS-CoV-2 suggesting that EchA and SpinA may interact with Spike proteins drom both viruses. The results suggest that these pigments could act as inhibitors of S protein, pointing them as antiviral drugs for SARS-CoV-2.<br>

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