tetano
Editor, Senior Moderator
Heliyon
. 2021 Mar;7(3):e06572.
doi: 10.1016/j.heliyon.2021.e06572. Epub 2021 Mar 20.
Mutational analysis of structural proteins of SARS-CoV-2
Shweta Jakhmola[SUP] 1 [/SUP], Omkar Indari[SUP] 1 [/SUP], Dharmendra Kashyap[SUP] 1 [/SUP], Nidhi Varshney[SUP] 1 [/SUP], Ayan Das[SUP] 1 [/SUP], Elangovan Manivannan[SUP] 2 [/SUP], Hem Chandra Jha[SUP] 1 [/SUP]
Affiliations
Abstract
SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-?B, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.
Keywords: D614G; Integrin; Mutations; SARS-CoV-2; Signaling pathways; Spike protein.
. 2021 Mar;7(3):e06572.
doi: 10.1016/j.heliyon.2021.e06572. Epub 2021 Mar 20.
Mutational analysis of structural proteins of SARS-CoV-2
Shweta Jakhmola[SUP] 1 [/SUP], Omkar Indari[SUP] 1 [/SUP], Dharmendra Kashyap[SUP] 1 [/SUP], Nidhi Varshney[SUP] 1 [/SUP], Ayan Das[SUP] 1 [/SUP], Elangovan Manivannan[SUP] 2 [/SUP], Hem Chandra Jha[SUP] 1 [/SUP]
Affiliations
- PMID: 33778179
- PMCID: PMC7980187
- DOI: 10.1016/j.heliyon.2021.e06572
Abstract
SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-?B, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.
Keywords: D614G; Integrin; Mutations; SARS-CoV-2; Signaling pathways; Spike protein.