Document Type : Original Articles
Authors
1
Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
2
Department of Biotechnology, Behesht Aein Laboratory Complex, (MABA) No 193 Jalal Al Ahmad Avenue, Tehran, Iran.
3
Department of Genomics and Genetic Engineering, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
4
Department of Human Viral Vaccine, Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
10.22092/ari.2024.367733.3422
Abstract
At the end of 2019, an acute respiratory disease caused by a novel coronavirus known as SARS-CoV-2 (Covid19) emerged in Wuhan, China. This disease spread rapidly across cities in China and also to other countries worldwide. Many countries were compelled to develop and manufacture vaccines, antigens, testing kits, and antiviral medications to mitigate mortality rates. Severe acute respiratory syndrome coronavirus2(SARS-CoV2 or Covid19) uses its spike (S) protein to enable the virus to enter host cells. The viral entry process is linked to the cleavage of the spike (S) protein at the S1|S2site. This cleavage can take place either at the plasma membrane of the host cell, known as the early pathway, or within the endosomal membrane, referred to as the late pathway, which is determined by the type of host cell involved. Previous research has identified a unique insertion in the S2 region of Covid-19, which may enhance the virus's ability to target cells that express the appropriate proteases and receptors. 3D models of the SARS-CoV and (SARS-CoV2 or Covid19) Spike-proteins (S-Protein) were constructed, analyzed, and evaluated using the SARS-CoV Spike-structure (PDB No.5X58) as a reference. The structure of CoVs models was reviewed using the online Cn3D V4.3.1 software. Additionally, CoVs sequences were analyzed utilizing the PiTou V3.0.2 software. Bioinformatics simulation results indicated that the majority of structural mutations enhancing the efficiency and activity of the S2 subunit were located at the cleavage site (CVs), within the C-terminal region spanning from 654 to 691. Utilizing bioinformatics tools, an analysis of mutations was conducted within the S2 subunit at the excision site and C-terminal region in related CoVs. Additionally, it provided insights into the origin of mutations such as furin and cleavage sites (CVs) in Covid19 and compared them with other CoVs. Most of the mutations that increase the aggressiveness of the S2 subunit were observed in the S2 C-terminal and cleavage site (CVs). Research has shown furin and some other proteases are involved in processing these mutations. Among these, the Transmembrane Serine Protease 2(TMPRSS2) plays a key role in facilitating viral entry via the early pathway.
Keywords
Main Subjects
)