scholarly journals Smoking May Increase the Risk of COVID-19 Infection: Evidence from In Silico Analysis

2021 ◽  
pp. 12-21
Author(s):  
Qazi Mohammad Sajid Jamal ◽  
Saif Khan ◽  
Mahvish Khan ◽  
Awais Abrar Ansai ◽  
Jalaluddin Mohammad Ashraf ◽  
...  
Keyword(s):  
Hydrogen Bonds ◽  
Protein Interaction ◽  
In Silico ◽  
Respiratory Infections ◽  
In Silico Analysis ◽  
Respiratory Illness ◽  
Protein Docking ◽  
Spike Protein ◽  
Chemical Database ◽  
Nicotine Consumption

Introduction: SARS-CoV2, first reported in December 2019 in Wuhan as COVID-19 causing respiratory illness, rapidly evolved into a pandemic owing to its very high infectivity. There is insufficient evidence about if and how smoking affects the risk of COVID-19 infection, and the reports on whether smoking increases or reduces the risk of respiratory infections, are contradictory. Therefore, the current study was designed to determine the effects of nicotine consumption on the infectivity of COVID-19. Methods: We performed in silico computer simulation-based study. The structures of SARS-CoV2spike ectodomain, and its receptor ACE2, were obtained from PDB. The structure of nicotine and its metabolites NNK and NNAL were obtained from the PubChem chemical database. After optimization, they were interacted using AutoDock 4.2, to see the effect of nicotine, NNK, or NNAL presence on the docking of viral spike protein to its receptor ACE2. Results: ACE2 vs spike protein interaction results were used as a control (ZDOCK score 1498.484, with four hydrogen bonds). The NNK+ACE2 vs spike protein docking formed 10 hydrogen bonds with the highest ZDOCK score of 1515.564. NNAL+ ACE2 vs spike protein interaction formed eleven hydrogen bonds with the ZDOCK score of 1499.371. Nicotine+ACE2 vs spike protein docking showed the lowest ZDOCK score of 1496.302 and formed 8 hydrogen bonds. Whereas, NNK+spike vs ACE2 interaction had a ZDOCK score of 1498.490 and formed eight hydrogen bonds. NNAL+spike vs ACE2 docking formed eleven hydrogen bonds with a ZDOCK score of 1498.482. And Nicotine+spike vs ACE2 interaction showed a ZDOCK score of 1498.488 and formed 9 hydrogen bonds. Conclusions: The binding of nicotine to either spike of virus or its receptor ACE2 is not affecting the viral docking with the receptor. But binding of NNK, a metabolite of nicotine, is facilitating the viral docking with its receptor indicating that smoking may increase the risk of COVID-19 infection.

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 Elucidation of the interactions between SARS-CoV-2 Spike protein and wild and mutant types of IFITM proteins by in silico methods

2021 ◽  
Author(s):  
Nazli Irmak Giritlioglu ◽  
Gizem Koprululu Kucuk
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Protein Complexes ◽  
Protein Product ◽  
Binding Energies ◽  
Spike Protein ◽  
Web Based

COVID-19 is a viral disease that has been a threat to the whole world since 2019. Although effective vaccines against the disease have been developed, there are still points to be clarified about the mechanism of SARS-CoV-2, which is the causative agent of COVID-19. In this study, we determined the binding energies and the bond types of complexes formed by open (6VYB) and closed (6VXX) forms of the Spike protein of SARS-CoV-2 and wild and mutant forms of IFITM1, IFITM2, and IFITM3 proteins using the molecular docking approach. First, all missense SNPs were found in the NCBI Single Nucleotide Polymorphism database (dbSNP) for IFITM1, IFITM2, and IFITM3 and analyzed with SIFT, PROVEAN, PolyPhen-2, SNAP2, Mutation Assessor, and PANTHER cSNP web-based tools to determine their pathogenicity. When at least four of these analysis tools showed that the SNP had a pathogenic effect on the protein product, this SNP was saved for further analysis. Delta delta G (DDG) and protein stability analysis for amino acid changes were performed in the web-based tools I-Mutant, MUpro, and SAAFEC-SEQ. The structural effect of amino acid change on the protein product was made using the HOPE web-based tool. HawkDock server was used for molecular docking and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) analysis and binding energies of all complexes were calculated. BIOVIA Discovery Studio program was utilized to visualize the complexes. Hydrogen bonds, salt bridges, and non-bonded contacts between Spike and IFITM protein chains in the complexes were detected with the PDBsum web-based tool. The best binding energy among the 6VYB-IFITM wild protein complexes belong to 6VYB-IFITM1 (-46.16 kcal/mol). Likewise, among the 6VXX-IFITM wild protein complexes, the most negative binding energy belongs to 6VXX-IFITM1 (-52.42 kcal/mol). An interesting result found in the study is the presence of hydrogen bonds between the cytoplasmic domain of the IFITM1 wild protein and the S2 domain of 6VYB. Among the Spike-IFITM mutant protein complexes, the best binding energy belongs to the 6VXX-IFITM2 N63S complex (-50.77 kcal/mol) and the worst binding energy belongs to the 6VXX-IFITM3 S50T complex (4.86 kcal/mol). The study suggests that IFITM1 protein may act as a receptor for SARS-CoV-2 Spike protein. Assays must be advanced from in silico to in vitro for the determination of the receptor-ligand interactions between IFITM proteins and SARS-CoV-2.

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.

The failure to meet GMP on completely eliminating replication-competent adenoviruses in vaccines using the chimpanzees Adv will have disastrous consequences, since it is closest to HAdv species E known to cause respiratory and ocular disease

2021 ◽  
Author(s):  
Sandeep Chakraborty
Keyword(s):  
United States ◽  
Adenoviral Vector ◽  
Respiratory Infections ◽  
Respiratory Illness ◽  
The United States ◽  
Ocular Disease ◽  
Lung Damage ◽  
Spike Protein ◽  
Live Virus ◽  
Vector Vaccine

Chimpanzee adenovirus (Y25, Accid:JN254802.1) is being used in the ChAdOx1-nCOV (Covishield) vaccine [1] because it has low human seroprevalence [2].Closest to HAdV4 - respiratory and ocular disease causing speciesThis virus is closest to (95.36% identity, Accid:KX384949.1) to those found in HAdV4 respiratory infections with a ‘concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees’ [3]. In fact, it was first ‘identified by its association with outbreaks of acute respiratory disease in military recruits’ in the 1950’s [4]. A recent paper noted that ‘increasing infections among civilians are a matter of concern’ [5], including an outbreak of respiratory illness on 5 college campuses in the United States (2018-19) [6]. Also, 15 new HAdV-E4 strains were extracted from cases of respiratory and ocular disease in the US and Japan, indicating the cell specificity of this species [7].What cells will this adenovirus infect?The fiber protein [8] (the spike protein equivalent of the SARS-Cov2 virus) shows very high homology in the N-termimal (Fig. 1). There is no characterization of the human cells this Chimpanzee adenoviral-vector will infect to make Cov2 spike protein - but it surely will be respiratory and ocular cells.Previously, I have raised concern that the replication-deficient adenoviral vector, used to deliver SARS- Cov2 spike protein as a vaccine, could recombine with the homologous human adenoviral to generate a novel adenovirus+spike virus [9].Failure to remove the E1 gene would leave a live virus in the vaccineThe vector vaccine production process (making millions of doses) has known issues, especially the ‘rare appearance of replication-competent adenovirus’ [10], requiring strict GMP-compliance [11]. Brazil has raised similar concerns about the adenovirus-vectored-vaccine from Russia(Sputnik) [12]. This is essentially the E1 replication gene - which is supposed to be absent - but could be picked up from the human cell lines used to manufacture the vaccine doses. The failure to comply with this could lead to disastrous consequences, as these could cause all diseases the live virus could.How to detect - or stop thisMetagenomic studies could easily detect if such an event has occurred, while sequencing or PCR of the vaccine doses for the presence of the E1 gene could stop it from happening. Reports of negative Cov2 PCR with significant lung damage - or new symptoms like conjunctivitis strongly associated with this species of adenoviruses needs to be investigated in more depth

scholarly journals Myxobacterial Depsipeptide Chondramides Interrupt SARS-CoV-2 Entry by Targeting Its Broad, Cell Tropic Spike Protein: Antagonistic Prospects for Anti-COVID-19 Drug Discovery

2021 ◽  
Author(s):  
Rey Arturo T. Fernandez ◽  
Mark Tristan J. Quimque ◽  
Kin Israel Notarte ◽  
Joe Anthony Manzano ◽  
Delfin Yñigo H. Pilapil ◽  
...  
Keyword(s):  
Host Cell ◽  
In Silico ◽  
Protein Docking ◽  
Spike Protein ◽  
Viral Agent ◽  
Viral Attachment ◽  
Cell Receptors ◽  
Binding Domains ◽  
Neuropilin 1 ◽  
The Uk

The severity of the COVID-19 pandemic necessitated the search for drugs against the causative viral agent, SARS-CoV-2. Among the promising targets is the viral surface of SARS-CoV-2 adorned by spike proteins appearing as crown-like structures known for their function in viral attachment and entry mechanisms. To exploit the potential of previously reported antiviral microbial metabolites, we explored the antagonistic prospects of myxobacterial secondary metabolites against receptor-binding domains (RBD) to host cell receptors namely angiotensin-converting enzyme 2 (ACE2), basigin (CD147) and glucose-regulated protein 78 (GRP78) as well as the binding site of neuropilin-1 (NRP1) in the SARS-CoV-2 spike protein using in silico molecular interaction based approaches such as molecular and protein-protein docking along with an investigation of their pharmacokinetic profiles. Thus, the cyclic depsipeptide chondramides in general conferred high affinity and demonstrated strong binding to true viral hot spots in the spike protein such as Arg403, Gln493 and Gln498 with high selectivity compared to most of the host cell receptors studied. The binding energy (BE) of chondramide C3 (1), being the top ligand against ACE2 and CD147 RBD, remained relatively constant when docked against most of the spike variants such as A475V, L452R, V483A, S477N, F490L and V439K. On the other hand, the parent congener chondramide C (2) exhibited strong affinity against the UK variant (N501Y), the South African variant (E484K) and the globally prevalent D614G along with its co-occurring mutation in the RBD, I472V. Meanwhile, chondramide C6 (29) showed highest BE towards GRP78 RBD. To study the effect of complexed chondramide ligands, protein-protein binding experiments were carried out using high-ambiguity driven docking (HADDOCK) which showed weaker binding affinity between spike and the target host receptors. The in silico active chondramides in general conferred favourable pharmacokinetic properties illustrating their potential to be developed as anti-COVID-19 drugs that limit viral attachment and minimize infection.

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 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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