Your browser doesn't support javascript.
SARS-CoV-2 Fusion Peptide has a Greater Membrane Perturbating Effect than SARS-CoV with Highly Specific Dependence on Ca2.
Lai, Alex L; Freed, Jack H.
  • Lai AL; ACERT, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States.
  • Freed JH; ACERT, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, United States. Electronic address: jhf3@cornell.edu.
J Mol Biol ; 433(10): 166946, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1386061
Semantic information from SemMedBD (by NLM)
1. Study USES Sequence Alignment
Subject
Study
Predicate
USES
Object
Sequence Alignment
2. FES wt Allele|FDPS|FES STIMULATES calcium ion
Subject
FES wt Allele|FDPS|FES
Predicate
STIMULATES
Object
calcium ion
3. FES wt Allele|FDPS|FES INTERACTS_WITH Ions
Subject
FES wt Allele|FDPS|FES
Predicate
INTERACTS_WITH
Object
Ions
4. calcium ion AFFECTS Virus Internalization
Subject
calcium ion
Predicate
AFFECTS
Object
Virus Internalization
5. Study USES Sequence Alignment
Subject
Study
Predicate
USES
Object
Sequence Alignment
6. FES wt Allele|FDPS|FES STIMULATES calcium ion
Subject
FES wt Allele|FDPS|FES
Predicate
STIMULATES
Object
calcium ion
7. FES wt Allele|FDPS|FES INTERACTS_WITH Ions
Subject
FES wt Allele|FDPS|FES
Predicate
INTERACTS_WITH
Object
Ions
8. calcium ion AFFECTS Virus Internalization
Subject
calcium ion
Predicate
AFFECTS
Object
Virus Internalization
ABSTRACT
Coronaviruses are a major infectious disease threat, and include the zoonotic-origin human pathogens SARS-CoV-2, SARS-CoV, and MERS-CoV (SARS-2, SARS-1, and MERS). Entry of coronaviruses into host cells is mediated by the spike (S) protein. In our previous ESR studies, the local membrane ordering effect of the fusion peptide (FP) of various viral glycoproteins including the S of SARS-1 and MERS has been consistently observed. We previously determined that the sequence immediately downstream from the S2' cleavage site is the bona fide SARS-1 FP. In this study, we used sequence alignment to identify the SARS-2 FP, and studied its membrane ordering effect. Although there are only three residue differences, SARS-2 FP induces even greater membrane ordering than SARS-1 FP, possibly due to its greater hydrophobicity. This may be a reason that SARS-2 is better able to infect host cells. In addition, the membrane binding enthalpy for SARS-2 is greater. Both the membrane ordering of SARS-2 and SARS-1 FPs are dependent on Ca2+, but that of SARS-2 shows a greater response to the presence of Ca2+. Both FPs bind two Ca2+ ions as does SARS-1 FP, but the two Ca2+ binding sites of SARS-2 exhibit greater cooperativity. This Ca2+ dependence by the SARS-2 FP is very ion-specific. These results show that Ca2+ is an important regulator that interacts with the SARS-2 FP and thus plays a significant role in SARS-2 viral entry. This could lead to therapeutic solutions that either target the FP-calcium interaction or block the Ca2+ channel.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Cell Membrane / Viral Fusion Proteins / Calcium / SARS Virus / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Language: English Journal: J Mol Biol Year: 2021 Document Type: Article Affiliation country: J.JMB.2021.166946

Full text: Available Collection: International databases Database: MEDLINE Main subject: Cell Membrane / Viral Fusion Proteins / Calcium / SARS Virus / Spike Glycoprotein, Coronavirus / SARS-CoV-2 Type of study: Prognostic study Language: English Journal: J Mol Biol Year: 2021 Document Type: Article Affiliation country: J.JMB.2021.166946