The heptad repeat region is a major selection target in MERS-CoV and related coronaviruses

• DOI: 10.1038/srep14480
• Publication Date: 2015-09-25T09:47:45Z
• Authors: Diego Forni; Giulia Filippi; Rachele Cagliani; Luca De Gioia; Uberto Pozzoli; Nasser Al-Daghri; Mario Clerici; Manuela Sironi
• Keywords: Heptad repeat; Coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) originated in bats and spread to humans via zoonotic transmission from camels. We analyzed the evolution of spike (S) gene betacoronaviruses (betaCoVs) isolated different mammals, bat populations, as well MERS-CoV strains current outbreak. Results indicated several positively selected sites located region comprising two heptad repeats (HR1 HR2) their linker. Two (R652 V1060) were betaCoVs phylogeny correspond mutations associated with expanded host range other coronaviruses. During most recent MERS-CoV, adaptive HR1 (Q/R/H1020) arose camels or a previous humans. determined that residues at position 1020 establish distinct inter- intra-helical interactions affect stability six-helix bundle formed by HRs. A similar effect on was observed for nearby mutation (T1015N) increases infection efficiency vitro. Data herein indicate repeat major target MERS-CoV-related viruses; these results are relevant design fusion inhibitor peptides antiviral function.