Molecular dynamics of Middle East Respiratory Syndrome Coronavirus (MERS CoV) fusion heptad repeat trimers

Abstract

Structural studies related to Middle East Respiratory Syndrome Coronavirus (MERS CoV) infection process are so limited. In this study, molecular dynamics (MD) simulations were carried out to unravel changes in the MERS CoV heptad repeat domains (HRs) and factors affecting fusion state HR stability. Results indicated that HR trimer is more rapidly stabilized, having stable system energy and lower root mean square deviations (RMSDs). While trimers were the predominant active form of CoVs HRs, monomers were also discovered in both of viral and cellular membranes. In order to find the differences between S2 monomer and trimer molecular dynamics, S2 monomer was modelled and subjected to MD simulation. In contrast to S2 trimer, S2 monomer was unstable, having high RMSDs with major drifts above 8 Å. Fluctuation of HR residue positions revealed major changes in the C-terminal of HR2 and the linker coil between HR1 and HR2 in both monomer and trimer. Hydrophobic residues at the a and d positions of HR helices stabilize the whole system, with minimal changes in RMSD. The global distance test and contact area difference scores support instability of MERS CoV S2 monomer. Analysis of HR1-HR2 inter-residue contacts and interaction energy revealed three energy scales along HR helices. Two strong interaction energies were identified at the start of the HR2 helix and at the C-terminal of HR2. The identified critical residues by MD simulation and residues at the a and d positions of HR helix were strong stabilizers of HR recognition.

Relationship between betacoronaviruses and the endocrine system: a new key to understand the COVID-19 pandemic—A comprehensive review

“…Some authors wondered whether hormonal treatment of COVID-19 patients may affect ACE2 expression in tissues and, as a consequence, viral spread. To date, some evidences ArƟcles on viral effect in endocrine Ɵssues (n=44) Similarities between SARS-CoV-2 and other betacoronaviridae [5] Chen Y (2020) [10] Hoffmann M (2020) [21] Siddell SG (2005) [22] Cavanagh D (1995) [23] Kandeel M (2018) [24] Risco C (1996) [25] Ruch T (2012) [26] Neuman BW (2011) [27] Chan JFW (2020) [28] Rabaan AA (2020) [29] Xu J (2020) [30] Li W (2003) [31] Matsuyama S (2010) [32] Shulla A (2011) [33] Zhang C (2020) [34] Zhou P (2020) [35] Fehr AR (2015) ACE2 and TMPRSS2 expression in endocrine tissues [11] Chen Y (2020) [12] Lazartigues E (2020) [63] Hamming I (2004) [64] Chi M (2020) [100] Reis FM (2011) [101] Jing Y (2020) [102] Goad J (2020) [103] Wang Z (2020) [104] Fan C (2020) Guo Y (2008) [67] Yao XH (2020) [77] Conti P (2020) [99] Giannis D (2020) indicate that both vitamin D and glucocorticoids may increase the systemic expression of ACE2 receptors [36][37][38]. However, according to these data, this increase in potential sites for viral entry is only apparently disadvantageous, rather it is essential to preserve the integrity of the parenchyma of various tissues, including endocrine glands.…”

From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes

“…CoVs are enveloped, positive‐stranded RNA viruses possessing a comparatively large genome approaching 30 kb and comprising four structural proteins, namely, spike (S), nucleocapsid (N) envelope (E), and membrane (M) 8 . The S protein is responsible for virus attachment to the receptor and fusion with cell membrane 9,10 . The N protein interacts with the viral RNA to form the ribonucleoprotein 11 .…”

Molecular Basis of Pathogenesis of Coronaviruses: A Comparative Genomics Approach to Planetary Health to Prevent Zoonotic Outbreaks in the 21st Century

“…The four structural proteins contribute to the development of viral structural features as their name suggests. Spike protein mediates the attachment of the virus to the host receptors leading to their fusion with the cell membrane (Kandeel et al, 2018;Siddell, 1995). N-protein synthesizes nucleocapsid of the virus by interacting with the viral mRNA for the formation of ribonucleoprotein (Risco et al, 1996).…”