COVID-19 spike-host cell receptor GRP78 binding site prediction

Ibrahim, Ibrahim M.; Abdelmalek, Doaa H.; El-Shahat, Mohammed; Elfiky, Abdo A.

doi:10.1016/j.jinf.2020.02.026

Cited by 440 publications

(419 citation statements)

References 30 publications

Supporting

Mentioning

401

Contrasting

Unclassified

Order By: Relevance

“…These numbers are continually increasing each day, and the number of confirmed cases at the time of this writing has now exceeded 258,000, with 11,268 confirmed deaths, mostly in China, Europe, and the Islamic Republic of Iran. On 20 January 2020, the National Health Commission of China confirmed human-to-human transmission of the COVID-J o u r n a l P r e -p r o o f Based on its nucleotide sequences, SARS-CoV-2 is a member of Betacoronaviruses, such as the SARS and MERS HCoVs (Chan et al , 2015, Ibrahim et al , 2020.…”

Section: Introductionmentioning

confidence: 99%

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

2020

Self Cite

View full text Add to dashboard Cite

Journal Pre-proof J o u r n a l P r e -p r o o f Abstract Aims: A new human coronavirus (HCoV), which has been designated SARS-CoV-2, began spreading in December 2019 in Wuhan City, China causing pneumonia called COVID-19.The spread of SARS-CoV-2 has been faster than any other coronaviruses that have succeeded in crossing the animal-human barrier. There is concern that this new virus will spread around the world as did the previous two HCoVs-Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)-each of which caused approximately 800 deaths in the years 2002 and 2012, respectively. Thus far, 11,268 deaths have been reported from the 258,842 confirmed infections in 168 countries. Main methods: In this study, the RNA-dependent RNA polymerase (RdRp) of the newly emerged coronavirus is modeled, validated, and then targeted using different anti-polymerase drugs currently on the market that have been approved for use against various viruses. Key findings: The results suggest the effectiveness of Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir as potent drugs against SARS-CoV-2 since they tightly bind to its RdRp. In addition, the results suggest guanosine derivative (IDX-184), Setrobuvir, and YAK as top seeds for antiviral treatments with high potential to fight the SARS-CoV-2 strain specifically. Significance: The availability of FDA-approved anti-RdRp drugs can help treat patients and reduce the danger of the mysterious new viral infection COVID-19. The drugs mentioned above can tightly bind to the RdRp of the SARS-CoV-2 strain and thus may be used to treat the disease. No toxicity measurements are required for these drugs since they were previously tested prior to their approval by the FDA. Keywords Journal Pre-proof J o u r n a l P r e -p r o o f COVID-19; SARS-CoV-2; RdRp; molecular docking; structural bioinformatics; drug repurposing 19 outbreak (Yang, 2020). Ten days later, the WHO declared COVID-19 to be a Public Health Emergency of International Concern (PHEIC), then COVID-19 is declared as a pandemic 40 days later by the WHO. The symptoms of COVID-19 include fever, malaise, dry cough, shortness of breath, and respiratory distress (Hui et al., 2020). Journal Pre-proof drugs, either currently on the market or in clinical trials, to stop the infection immediately. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir showed promising results for use against the newly emerged strain of coronavirus. Besides, the IDX-184, Setrobuvir, and YAK compounds exhibited excellent results for binding SARS-CoV-2 RdRp. We suggest utilizing GTP as a seed to obtain specific inhibitors against SARS-CoV-2 RdRp using its high-quality model. Journal Pre-proof J o u r n a l P r e -p r o o f Acknowledgment: Mrs. Kauther M Shaltoot is appreciated for her kind help and support; without her, this work was not possible. Prof. Dr. Wael Elshemey is appreciated for guidance and performing the docking calculations on his computational facility.

show abstract

Section: Introductionmentioning

confidence: 99%

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent in vitro reports have demonstrated that similar host proteins are involved in facilitating cell entry by SARS-CoV-2, such as ACE2 and TMPRSS2[5, 24] Biophysical and structural evidence strongly support an interaction of ACE2 with SARS-CoV-2 spike protein, similar to SARS-CoV spike protein[12, 13]. Molecular docking studies have also suggested that SARS-CoV-2 spike protein can interact with cell-surface GRP78[25]. Indirect evidence for a role of CD147 in SARS-CoV-2 binding has been demonstrated in vitro with the use of an anti-CD147 intervention that prevented virus replication[26].…”

Section: Introductionmentioning

confidence: 99%

Gene expression andin situprotein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

Aguiar

Tremblay

Mansfield

et al. 2020

Preprint

117

View full text Add to dashboard Cite

words):In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilizes ACE2 and TMPRSS2 host molecules for viral entry. ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection.Additional host molecules including ADAM17, cathepsin L, CD147, and GRP78 may also function as receptors for SARS-CoV-2.To determine the expression and in situ localization of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analyzed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung. We present confirmatory evidence for the presence of TMPRSS2, CD147, and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternate receptors for SARS-CoV-2 exist to facilitate initial host cell infection.In 2003, the severe acute respiratory syndrome (SARS) outbreak caused by the SARS coronavirus (CoV) resulted in 8096 probable cases with 774 confirmed deaths [1, 2] In patients with SARS, deaths were attributed to acute respiratory distress associated with diffuse bilateral pneumonia and alveolar damage [3]. In December 2019, SARS-CoV-2 emerged causing the COVID-19 pandemic. SARS-CoV-2 is spreading at a much more rapid rate than SARS-CoV [4][5][6]. Similar clinical reports of diffuse bilateral pneumonia and alveolar damage have been reported [7][8][9]. Severe cases of SARS-CoV-2 have been associated with infections of the lower respiratory tract with detection of the virus throughout this tissue as well as the upper respiratory tract [7][8][9]. The biological mechanisms that may govern differences in the number of SARS and COVID-19 cases remain undefined. It is possible that SARS-CoV-2 possesses distinct molecular mechanisms that impact the virulence through viral proteins, greater susceptibility of host cells to infection, permissivity of host cells to virus replication, or some combination of these and other potentially unknown factors [10][11][12][13]. Understanding SARS and SARS-CoV-2 virus similarities and differences at the molecular level in the host may provide insights into transmission, pathogenesis, and interventions.The seminal report identifying the receptor for SARS-CoV used a HEK29...

show abstract

“…Infection can occur from animal to animal and from animal to human in the case of close contact with infected animals (Azhar et al, 2014;Han et al, 2016). Additionally human to human transmission was reported for human coronaviruses (Elfiky, 2020a(Elfiky, , 2020bIbrahim et al, 2020;Yang, 2020). SARS, MERS, and SARS-CoV-2 caused diseases are characterized by a lower respiratory ailment like bronchitis, bronchiolitis, and pneumonia, which leads to death with different ratios (Bogoch et al, 2020;Graham et al, 2013;van den Brand et al, 2015;Wu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective

Elfiky

Azzam

2020

Journal of Biomolecular Structure and Dynamics

Self Cite

View full text Add to dashboard Cite

The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp. ARTICLE HISTORY

show abstract

COVID-19 spike-host cell receptor GRP78 binding site prediction

Cited by 440 publications

References 30 publications

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study

Gene expression andin situprotein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue

Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective

Contact Info

Product

Resources

About