In silico Identification of Characteristics Spike Glycoprotein of SARS-CoV-2 in the Development Novel Candidates for COVID-19 Infectious Diseases

Abstract

Background: The emergence of infectious diseases caused by SARS-CoV-2 has resulted in more than 90,000 infections and 3,000 deaths. The coronavirus spike glycoprotein encourages the entry of SARS-CoV-2 into cells and is the main target of antivirals. SARS-CoV-2 uses ACE2 to enter cells with an affinity similar to SARS-CoV, correlated with the efficient spread of SARS-CoV-2 among humans.Objective: In the research, identification, evaluation, and exploration of the structure of SARS-CoV and SARS-CoV-2 spike glycoprotein macromolecules and their effects on Angiotensin-Converting Enzyme 2 (ACE-2) using in silico studies.Methods: The spike glycoproteins of the two coronaviruses were prepared using the BIOVIA Discovery Studio 2020. Further identification of the three-dimensional structure and sequencing of the macromolecular spike glycoprotein structure using Chimera 1.14 and Notepad++. To ensure the affinity and molecular interactions between the SARS-CoV and SARS-CoV-2 spike glycoproteins against ACE-2 protein-protein docking simulations using PatchDock was accomplished. The results of the simulations were verified using the BIOVIA Discovery Studio 2020.Results: Based on the results of the identification of the macromolecular structure of the spike glycoprotein, it was found that there are some similarities in characteristics between SARS-CoV and SARS-CoV-2. Protein-protein docking simulations resulted that SARS-COV-2 spike glycoprotein has the strongest bond with ACE-2, with an ACE score of −1509.13 kJ/mol.Conclusion: Therefore, some information obtained from the results of this research can be used as a reference in the development of SARS-CoV-2 spike glycoprotein inhibitor candidates for the treatment of infectious diseases of COVID-19.

In Silico and In Vitro Studies of Alchemilla viridiflora Rothm—Polyphenols’ Potential for Inhibition of SARS-CoV-2 Internalization

“…One of the key interacting residues, Gln160, was previously identified as one of 23 virus residues that participate in stable hydrogen bonds, which let the virus bind to the ACE2 receptor. Most of the tested A. viridiflora polyphenols showed interaction with this residue, and the second-most potent compound, tellimagrandin I, interacted with it via an H bond at a distance of 2.82Å (Figure 3) [22]. Two compounds from the ellagitannin class, tellimagrandin I and II, showed only a somewhat lower affinity for interacting with S-glycoprotein, with binding affinity energies of −8.022 and −7.955 kcal/mol, respectively.…”

“…One of the key interacting residues, Gln160, was previously identified as one of 23 virus residues that participate in stable hydrogen bonds, which let the virus bind to the ACE2 receptor. Most of the tested A. viridiflora polyphenols showed interaction with this residue, and the second-most potent compound, tellimagrandin I, interacted with it via an H bond at a distance of 2.82 Å (Figure 3) [22].…”

In silico design of refined ferritin-SARS-CoV-2 glyco-RBD nanoparticle vaccine

“…Coronaviruses are large enveloped RNA-positive-stranded viruses, and the SARS-CoV-2 consists of a large RNA genome, four structural proteins, 16 nonstructural proteins, and nine to 11 accessory proteins ( Michel et al, 2020 ; Redondo et al, 2021 ). The four structural proteins include the spike, envelope, membrane, and nucleocapsid proteins ( Chan et al, 2020 ; Walls et al, 2020 ; Tao et al, 2021 ), of which the spike glycoprotein (S-protein) is of particular interest for coronavirus vaccine target ( Bisht et al, 2004 ; Du et al, 2009 ; Fakih and Dewi, 2020 ; Yang et al, 2020 ).…”

“…The four structural proteins include the spike, envelope, membrane, and nucleocapsid proteins (Chan et al, 2020;Walls et al, 2020;Tao et al, 2021), of which the spike glycoprotein (S-protein) is of particular interest for coronavirus vaccine target (Bisht et al, 2004;Du et al, 2009;Fakih and Dewi, 2020;Yang et al, 2020).…”

Comparative analysis of the stability features of human alpha-defensins as candidates for the future COVID-19 therapy through molecular dynamics

“…It has a wide range of biological functions and can help to mitigate the negative effects of the RAS in a number of illnesses (Holly et al, 2017;Wilson et al, 2013). Because 2019-nCoV shares 79.5 percent of the total genomic sequence identity with SARS-CoV, the pathogenic mechanism of COVID-19 may be comparable to that of SARS (Fakih & Dewi, 2020). Although COVID-19 mediated by SARS-CoV-2 has a lower overall risk of mortality than SARS and MERS, severe symptoms typically encounter organ dysfunction, involving acute respiratory distress syndrome (ARDS), renal insufficiency failure, adverse cardiac injury, and severe hepatic injury (Ni et al, 2020).…”